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Title:
Fever and the thermal regulation of immunity: the immune system feels the heat
Authors:
Evans, Sharon S.; Repasky, Elizabeth A.; Fisher, Daniel T.
Abstract:
Fever is a cardinal response to infection that has been conserved in warm and cold-blooded vertebrates for over 600 million years of evolution. The fever response is executed by integrated physiological and neuronal circuitry and confers a survival benefit during infection. Here, we review our current understanding of how the inflammatory cues delivered by the thermal element of fever stimulate innate and adaptive immune responses. We further highlight the unexpected multiplicity of roles of the pyrogenic cytokine interleukin-6 (IL-6), both during fever induction as well as during the mobilization of lymphocytes to the lymphoid organs that are the staging ground for immune defence. Finally, we discuss the emerging evidence that suggests the adrenergic signalling pathways associated with thermogenesis shape immune cell function.
Published:
2015-06
Title:
Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline <i>CDH1</i> mutation carriers
Authors:
van der Post, Rachel S; Vogelaar, Ingrid P; Carneiro, Fátima; Guilford, Parry; Huntsman, David; Hoogerbrugge, Nicoline; Caldas, Carlos; Chelcun Schreiber, Karen E; Hardwick, Richard H; Ausems, Margreet G E M; Bardram, Linda; Benusiglio, Patrick R; Bisseling, Tanya M; Blair, Vanessa; Bleiker, Eveline; Boussioutas, Alex; Cats, Annemieke; Coit, Daniel; DeGregorio, Lynn; Figueiredo, Joana; Ford, James M; Heijkoop, Esther; Hermens, Rosella; Humar, Bostjan; Kaurah, Pardeep; Keller, Gisella; Lai, Jennifer; Ligtenberg, Marjolijn J L; O'Donovan, Maria; Oliveira, Carla; Pinheiro, Hugo; Ragunath, Krish; Rasenberg, Esther; Richardson, Susan; Roviello, Franco; Schackert, Hans; Seruca, Raquel; Taylor, Amy; ter Huurne, Anouk; Tischkowitz, Marc; Joe, Sheena Tjon A; van Dijck, Benjamin; van Grieken, Nicole C T; van Hillegersberg, Richard; van Sandick, Johanna W; Vehof, Rianne; van Krieken, J Han; Fitzgerald, Rebecca C
Abstract:
Published:
2015-06
Title:
Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid 16:4(n-3) After Consumption of Fish and Fish Oil
Authors:
Daenen, Laura G. M.; Cirkel, Geert A.; Houthuijzen, Julia M.; Gerrits, Johan; Oosterom, Ilse; Roodhart, Jeanine M. L.; van Tinteren, Harm; Ishihara, Kenji; Huitema, Alwin D. R.; Verhoeven-Duif, Nanda M.; Voest, Emile E.
Abstract:
IMPORTANCE: Our research group previously identified specific endogenous platinum-induced fatty acids (PIFAs) that, in picomolar quantities, activate splenic macrophages leading to resistance to chemotherapy in mouse models. Fish oil was shown to contain the PIFA 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) and when administered to mice neutralized chemotherapy activity. OBJECTIVE: Because patients with cancer frequently use fish oil supplements, we set out to determine exposure to 16:4(n-3) after intake of fish or fish oil. DESIGN, SETTING, AND PARTICIPANTS: (1) In November 2011, 400 patients with cancer undergoing treatment at the University Medical Center Utrecht were surveyed to determine their use of fish oil supplements; 118 patients responded to the questionnaire (30%); (2) pharmacokinetic analysis of the 16:4(n-3) content of 6 fish oils and 4 fishes was carried out; (3) from April through November 2012, a healthy volunteer study was performed to determine 16:4(n-3) plasma levels after intake of 3 different brands of fish oil or 4 different fish species. Thirty healthy volunteers were randomly selected for the fish oil study; 20 were randomly selected for the fish study. These studies were supported by preclinical tumor experiments in mice to determine chemoresistance conducted between September 2011 and December 2012. MAIN OUTCOMES AND MEASURES: (1) Rate of use of fish oil supplements among patients undergoing cancer treatment at our institution; (2) levels of 16:4(n-3) present in 3 brands of fish oil and 4 species of fish; and (3) plasma levels of 16:4(n-3) present in healthy volunteers after consuming fish oil or fish. RESULTS: Eleven percent of respondents reported using omega-3 supplements. All fish oils tested contained relevant amounts of 16:4(n-3), from 0.2 to 5.7 µM. Mouse experiments showed that addition of 1 µL of fish oil to cisplatin was sufficient to induce chemoresistance, treatment having no impact on the growth rate of tumors compared with vehicle-treated controls (estimated tumor volume difference, 44.1 mm3; P > .99). When the recommended daily amount of 10 mL of fish oil was administered to healthy volunteers, rises in plasma 16:4(n-3) levels were observed, reaching up to 20 times the baseline levels. Herring and mackerel contained high levels of 16:4(n-3) in contrast to salmon and tuna. Consumption of fish with high levels of 16:4(n-3) also resulted in elevated plasma levels of 16:4(n-3). CONCLUSIONS AND RELEVANCE: All tested fish oils and herring and mackerel fishes contained relevant levels of fatty acid 16:4(n-3), a fatty acid with chemotherapy-negating effects in preclinical models. After ingestion of these fish oils or fishes, 16:4(n-3) was rapidly taken up in the plasma of human volunteers. Until further data become available, fish oil and fish containing high levels of 16:4(n-3) may best be avoided on the days surrounding chemotherapy.
Published:
2015-06
Title:
Mitochondria: The ketogenic diet—A metabolism-based therapy
Authors:
Vidali, Silvia; Aminzadeh, Sepideh; Lambert, Bridget; Rutherford, Tricia; Sperl, Wolfgang; Kofler, Barbara; Feichtinger, René G.
Abstract:
a b s t r a c t Mitochondria are the energy-producing organelles of the cell, generating ATP via oxidative phosphory-lation mainly by using pyruvate derived from glycolytic processing of glucose. Ketone bodies generated by fatty acid oxidation can serve as alternative metabolites for aerobic energy production. The ketogenic diet, which is high in fat and low in carbohydrates, mimics the metabolic state of starvation, forcing the body to utilize fat as its primary source of energy. The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for " rare diseases " of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the keto-genic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment.
Published:
2015-06
Title:
Obesity-Induced Lymphedema: Clinical and Lymphoscintigraphic Features
Authors:
Greene, Arin; Grant, Frederick; Slavin, Sumner; Maclellan, Reid
Abstract:
Summary:The purpose of this study was to characterize obesity as a novel cause of lower extremity lymphedema. Fifty-one patients with a body mass index greater than 30 kg/m2 without any potential cause of lymphedema were evaluated with lymphoscintigraphy. Group 1 patients (n = 33) were at their maxi
Published:
2015-06
Title:
Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism
Authors:
Duivenvoorde, Loes P. M.; van Schothorst, Evert M.; Derous, Davina; van der Stelt, Inge; Masania, Jinit; Rabbani, Naila; Thornalley, Paul J.; Keijer, Jaap
Abstract:
Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-invasive challenge test that measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. To test whether OxR can be used to reveal early diet-induced health effects, we exposed mice to a low-fat (LF) or high-fat (HF) diet for only 5 days. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and epididymal white adipose tissue (eWAT) and serum markers for e.g. protein glycation and oxidation. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR; however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. Cumulatively, OxR is a promising new method to test food products on potential beneficial effects for human health.
Published:
2015-06
Title:
Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations
Authors:
Pastore, Robert L.; Brooks, Judith T.; Carbone, John W.
Abstract:
Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P
Published:
2015-06
Title:
The palaeo-environmental history of Big Willum Swamp, Weipa: An environmental context for the archaeological record
Authors:
Stevenson, Janelle; Brockwell, Sally; Rowe, Cassandra; Proske, Ulrike; Shiner, Justin
Abstract:
The environmental history of Big Willum (Waandriipayn) Swamp and the surrounding landscape is reconstructed for the last 8000 years through the analysis of pollen, charcoal and mineral magnetics. The data provide a Holocene record of vegetation and fire in an area where few records exist. Swamp initiation at Big Willum began prior to 8000 cal. BP, with swamp-like conditions maintained until 2200 cal. BP, after which it became a permanent deep water body, reaching its present day extent between 600-400 cal. BP. From 7000-1200 cal. BP the surrounding woodland was essentially stable. Fire is present throughout the record, with only one period of pronounced burning outside of the historic period, at around 1000 cal. BP, leading to a slightly more open understorey/woodland. The hydrological change at 2200 cal. BP that led to Big Willum becoming a more permanent water body overlaps with the end of the most intensive period of shell mound formation and the commencement of earth mound building at nearby Wathayn. This is suggestive that change in, or diversification of, mound types may in part be linked to environmental transformations in the late Holocene. One possibility is that greater water security allowed for increasing and more permanent exploitation of inland locations.
Published:
2015-06
Title:
Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior
Authors:
Patrick, Rhonda P.; Ames, Bruce N.
Abstract:
Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction.
Published:
2015-06
Title:
Adiponectin: an adipokine with protective features against metabolic syndrome
Authors:
Esfahani, Maryam; Movahedian, Ahmad; Baranchi, Mostafa; Goodarzi, Mohammad Taghi
Abstract:
Metabolic syndrome (MetS) as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases.
Published:
2015-05
Title:
Association of decrease in carbohydrate intake with reduction in abdominal fat during 3-month moderate low-carbohydrate diet among non-obese Japanese patients with type 2 diabetes
Authors:
Sasakabe, Tae; Haimoto, Hajime; Umegaki, Hiroyuki; Wakai, Kenji
Abstract:
OBJECTIVE: The effectiveness of a moderate low-carbohydrate diet (M-LCD) has been demonstrated in terms of glycemic control, body weight and serum lipid profiles. We investigated the effect of a 3-month M-LCD on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and examined an association between decrease in carbohydrate intake and reduction in abdominal fat among patients with Type 2 diabetes mellitus (T2DM). METHODS: Seventy-six patients (45 men and 31 women; mean age ± SD: 59.5 ± 11.1 years) with T2DM were instructed to follow an M-LCD for 3 months. We assessed abdominal fat distribution using computed tomography and macronutrient intakes from 3-day dietary records at baseline and after 3 months. RESULTS: The patients complied well with the M-LCD - %carbohydrate: %fat: %protein at baseline and after 3 months were 51:27:15 and 41:33:18 in men and 54:27:16 and 42:37:19 in women, respectively. VAT and SAT significantly decreased during the 3 months (P for time
Published:
2015-05
Title:
Comparison of correlates of bone mineral density in individuals adhering to lacto-ovo, vegan, or omnivore diets: a cross-sectional investigation
Authors:
Knurick, Jessica R.; Johnston, Carol S.; Wherry, Sarah J.; Aguayo, Izayadeth
Abstract:
Vegetarian diets are associated with factors that may not support bone health, such as low body mass and low intakes of protein; yet, these diets are alkaline, a factor that favors bone mineral density (BMD). This study compared the correlates of BMD in young, non-obese adults consuming meat-based (n = 27), lacto-ovo vegetarian (n = 27), or vegan (n = 28) diets for >=1 year. A 24 h diet recall, whole body DXA scan, 24 h urine specimen, and fasting blood sample were collected from participants. BMD did not differ significantly between groups. Protein intake was reduced ~30% in individuals consuming lacto-ovo and vegan diets as compared to those consuming meat-based diets (68 +/- 24, 69 +/- 29, and 97 +/- 47 g/day respectively, p = 0.006); yet dietary protein was only associated with BMD for those following vegan diets. Urinary pH was more alkaline in the lacto-ovo and vegan groups versus omnivores (6.5 +/- 0.4, 6.7 +/- 0.4, and 6.2 +/- 0.4 respectively, p = 0.003); yet urinary pH was associated with BMD in omnivores only. These data suggest that plant-based diets are not detrimental to bone in young adults. Moreover, diet prescriptions for bone health may vary among diet groups: increased fruit and vegetable intake for individuals with high meat intakes and increased plant protein intake for individuals who follow a vegetarian diet plan.
Published:
2015-05
Title:
Effect of cheese consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials. [Review]
Authors:
de Goede, Janette; Geleijnse, Johanna M.; Ding, Eric L.; Soedamah-Muthu, Sabita S.
Abstract:
CONCLUSION: Despite the similar P/S ratios of hard cheese and butter, consumption of hard cheese lowers LDL-C and HDL-C when compared with consumption of butter. Whether these findings can be attributed to calcium, specific types of saturated fatty acids, or the food matrix of cheese warrants further research. . Copyright © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Published:
2015-05
Title:
Elevated Serum Advanced Glycation Endproducts in Obese Indicate Risk for the Metabolic Syndrome: A Link Between Healthy and Unhealthy Obesity?
Authors:
Uribarri, Jaime; Cai, Weijing; Woodward, Mark; Tripp, Elizabeth; Goldberg, Laurie; Pyzik, Renata; Yee, Kalle; Tansman, Laurie; Chen, Xue; Mani, Venkatesh; Fayad, Zahi A.; Vlassara, Helen
Abstract:
Context: Although obesity can predispose to the metabolic syndrome (MS), diabetes, and cardiovascular disease, not all obese subjects develop MS, hence the need for new indicators of risk for this syndrome. Advanced glycation end products (AGEs) correlate with factors involved in the MS, including inflammation and insulin resistance (IR). Because AGEs can be derived from food and are modifiable, it is important to determine whether they are a risk factor for MS. Objective: The objective of this study was to assess the association of endogenous and exogenous AGEs with MS criteria. Design: The following data were collected in a cross-sectional study of subjects with and without the MS: serum AGEs (sAGEs) and mononuclear cell AGEs, metabolites, pro- and antiinflammatory markers, body fat mass measures, including abdominal magnetic resonance imaging, and caloric and dietary AGE (dAGE) consumption. Setting: The study was conducted in the general community. Participants: Participants included 130 MS and 139 non-MS subjects of both sexes, older than 50 years. Results: sAGEs (ϵN-carboxymethyllysine, methylglyoxal) were markedly elevated in obese persons with more than one other MS criteria but not in obese without MS criteria. sAGEs directly correlated with markers of IR (HOMA) and inflammation (leptin, TNFα, RAGE) and inversely with innate defenses (SIRT1, AGE receptor 1 [AGER1], glyoxalase-I, adiponectin). sAGEs correlated with dAGEs but not with calories, nutrient consumption, or fat mass measures. Consumption of dAGE, but not of calories, was markedly higher in MS than in non-MS. Conclusion: High sAGEs, a modifiable risk factor for IR, may indicate risk for the MS, type 2 diabetes, and cardiovascular disease. High dietary AGE consumption and serum AGE levels may link healthy obesity to at-risk obesity.
Published:
2015-05
Title:
Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes
Authors:
Ericson, Ulrika; Hellstrand, Sophie; Brunkwall, Louise; Schulz, Christina-Alexandra; Sonestedt, Emily; Wallstrom, Peter; Gullberg, Bo; Wirfalt, Elisabet; Orho-Melander, Marju
Abstract:
CONCLUSIONS: Decreased T2D risk at high intake of high- but not of low-fat dairy products suggests that dairy fat partly could have contributed to previously observed protective associations between dairy intake and T2D. Meat intake was associated with increased risk independently of the fat content. Copyright © 2015 American Society for Nutrition.
Published:
2015-05
Title:
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
Authors:
Coffee and Caffeine Genetics Consortium; Cornelis, Marilyn C.; Byrne, Enda M.; Esko, Tõnu; Nalls, Michael A.; Ganna, Andrea; Paynter, Nina; Monda, Keri L.; Amin, Najaf; Fischer, Krista; Renstrom, Frida; Ngwa, Julius S.; Huikari, Ville; Cavadino, Alana; Nolte, Ilja M.; Teumer, Alexander; Yu, Kai; Marques-Vidal, Pedro; Rawal, Rajesh; Manichaikul, Ani; Wojczynski, Mary K.; Vink, Jacqueline M.; Zhao, Jing Hua; Burlutsky, George; Lahti, Jari; Mikkilä, Vera; Lemaitre, Rozenn N.; Eriksson, Joel; Musani, Solomon K.; Tanaka, Toshiko; Geller, Frank; Luan, Jian'an; Hui, Jennie; Mägi, Reedik; Dimitriou, Maria; Garcia, Melissa E.; Ho, Weang-Kee; Wright, Margaret J.; Rose, Lynda M.; Magnusson, Patrik Ke; Pedersen, Nancy L.; Couper, David; Oostra, Ben A.; Hofman, Albert; Ikram, Mohammad Arfan; Tiemeier, Henning W.; Uitterlinden, Andre G.; van Rooij, Frank Ja; Barroso, Inês; Johansson, Ingegerd; Xue, Luting; Kaakinen, Marika; Milani, Lili; Power, Chris; Snieder, Harold; Stolk, Ronald P.; Baumeister, Sebastian E.; Biffar, Reiner; Gu, Fangyi; Bastardot, François; Kutalik, Zoltán; Jacobs, David R.; Forouhi, Nita G.; Mihailov, Evelin; Lind, Lars; Lindgren, Cecilia; Michaëlsson, Karl; Morris, Andrew; Jensen, Majken; Khaw, Kay-Tee; Luben, Robert N.; Wang, Jie Jin; Männistö, Satu; Perälä, Mia-Maria; Kähönen, Mika; Lehtimäki, Terho; Viikari, Jorma; Mozaffarian, Dariush; Mukamal, Kenneth; Psaty, Bruce M.; Döring, Angela; Heath, Andrew C.; Montgomery, Grant W.; Dahmen, Norbert; Carithers, Teresa; Tucker, Katherine L.; Ferrucci, Luigi; Boyd, Heather A.; Melbye, Mads; Treur, Jorien L.; Mellström, Dan; Hottenga, Jouke Jan; Prokopenko, Inga; Tönjes, Anke; Deloukas, Panos; Kanoni, Stavroula; Lorentzon, Mattias; Houston, Denise K.; Liu, Yongmei; Danesh, John; Rasheed, Asif; Mason, Marc A.; Zonderman, Alan B.; Franke, Lude; Kristal, Bruce S.; International Parkinson’s Disease Genomics Consortium (IPDGC); North American Brain Expression Consortium (NABEC); UK Brain Expression Consortium (UKBEC); Karjalainen, Juha; Reed, Danielle R.; Westra, Harm-Jan; Evans, Michele K.; Saleheen, Danish; Harris, Tamara B.; Dedoussis, George; Curhan, Gary; Stumvoll, Michael; Beilby, John; Pasquale, Louis R.; Feenstra, Bjarke; Bandinelli, Stefania; Ordovas, Jose M.; Chan, Andrew T.; Peters, Ulrike; Ohlsson, Claes; Gieger, Christian; Martin, Nicholas G.; Waldenberger, Melanie; Siscovick, David S.; Raitakari, Olli; Eriksson, Johan G.; Mitchell, Paul; Hunter, David J.; Kraft, Peter; Rimm, Eric B.; Boomsma, Dorret I.; Borecki, Ingrid B.; Loos, Ruth Jf; Wareham, Nicholas J.; Vollenweider, Peter; Caporaso, Neil; Grabe, Hans Jörgen; Neuhouser, Marian L.; Wolffenbuttel, Bruce Hr; Hu, Frank B.; Hyppönen, Elina; Järvelin, Marjo-Riitta; Cupples, L. Adrienne; Franks, Paul W.; Ridker, Paul M.; van Duijn, Cornelia M.; Heiss, Gerardo; Metspalu, Andres; North, Kari E.; Ingelsson, Erik; Nettleton, Jennifer A.; van Dam, Rob M.; Chasman, Daniel I.
Abstract:
Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P
Published:
2015-05
Title:
Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion
Authors:
Bonner, Caroline; Kerr-Conte, Julie; Gmyr, Valéry; Queniat, Gurvan; Moerman, Ericka; Thévenet, Julien; Beaucamps, Cédric; Delalleau, Nathalie; Popescu, Iuliana; Malaisse, Willy J; Sener, Abdullah; Deprez, Benoit; Abderrahmani, Amar; Staels, Bart; Pattou, François
Abstract:
Published:
2015-05
Title:
Metabolic syndrome and its components as predictors of nonalcoholic fatty liver disease in a northern urban Han Chinese population: a prospective cohort study
Authors:
Zhang, Tao; Zhang, Chengqi; Zhang, Yongyuan; Tang, Fang; Li, Hongkai; Zhang, Qian; Lin, Haiyan; Wu, Shuo; Liu, Yanxun; Xue, Fuzhong
Abstract:
OBJECTIVES: To explore the longitudinal effect of metabolic syndrome (MetS) and its components on the development of non-alcoholic fatty liver disease (NAFLD) and to evaluate the significance of MetS and its components as early markers of NAFLD risk in a northern urban Han Chinese population. MATERIALS AND METHODS: A total of 15,791 cohort members without NAFLD at baseline were included in the current study between 2005 and 2011. The baseline characteristics of the cohort were compared by MetS status at baseline and NAFLD status after follow-up. Cox proportional hazards models were used to estimate the unadjusted or adjusted hazard ratios (HRs) for development of NAFLD among individuals with MetS compared with individuals without MetS at baseline. RESULTS: During 51,652 person-years of follow-up, 3913 (24.78%) new cases of NAFLD occurred between 2005 and 2011. In the unadjusted model, the HR (95% confidence interval [CI]) for NAFLD was 2.51 (2.30, 2.73). After adjusting for gender, age, diet, smoking status, and regular exercise, the HR was 1.94 (1.78, 2.13). Gender differences were observed, with adjusted HRs (95% CIs) of 1.89 (1.71, 2.09) and 1.72 (1.43, 2.07) among males and females, respectively. Compared with individuals without MetS components, the HRs were 1.92 (1.76, 2.09), 2.64 (2.40, 2.90) and 3.51 (3.15, 3.91) for individuals with one, two, or three or more MetS components, respectively. Moreover, participants with obesity or hyperlipidemia had a higher risk of NAFLD than patients with hypertension or hyperglycemia, with HRs of 2.03 (1.83, 2.25) for obesity, 1.94 (1.72, 2.19) for hyperlipidemia, and 3.01 (2.68, 3.37) for these factors in combination. CONCLUSION: The present study indicates that MetS and its components independently predict the risk of NAFLD in a northern urban Han Chinese population and suggests that people with MetS or its component should initiate lifestyle changes to prevent the development of NAFLD.
Published:
2015-05
Title:
Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species
Authors:
Julio-Amilpas, Alberto; Montiel, Teresa; Soto-Tinoco, Eva; Gerónimo-Olvera, Cristian; Massieu, Lourdes
Abstract:
Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury.
Published:
2015-05
Title:
Vegetarian dietary patterns and the risk of colorectal cancers
Authors:
Orlich, Michael J.; Singh, Pramil N.; Sabaté, Joan; Fan, Jing; Sveen, Lars; Bennett, Hannelore; Knutsen, Synnove F.; Beeson, W. Lawrence; Jaceldo-Siegl, Karen; Butler, Terry L.; Herring, R. Patti; Fraser, Gary E.
Abstract:
IMPORTANCE: Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established. OBJECTIVE: To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS: The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96,354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77,659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES: Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURES: The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages. RESULTS: During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81 (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals. CONCLUSIONS AND RELEVANCE: Vegetarian diets are associated with an overall lower incidence of colorectal cancers. Pescovegetarians in particular have a much lower risk compared with nonvegetarians. If such associations are causal, they may be important for primary prevention of colorectal cancers.
Published:
2015-05
Title:
A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients
Authors:
Schwarz, Ricarda; Reif, Andreas; Scholz, Claus-Jürgen; Weissflog, Lena; Schmidt, Brigitte; Lesch, Klaus-Peter; Jacob, Christian; Reichert, Susanne; Heupel, Julia; Volkert, Julia; Kopf, Juliane; Hilscher, Max; Weber, Heike; Kittel-Schneider, Sarah
Abstract:
OBJECTIVES: Methylphenidate (MPH) is a commonly used stimulant medication for treating attention-deficit/hyperactivity disorder (ADHD). Besides inhibiting monoamine reuptake there is evidence that MPH also influences gene expression directly. METHODS: We investigated the impact of MPH treatment on gene expression levels of lymphoblastoid cells derived from adult ADHD patients and healthy controls by hypothesis-free, genome-wide microarray analysis. Significant findings were subsequently confirmed by quantitative Real-Time PCR (qRT PCR) analysis. RESULTS: The microarray analysis from pooled samples after correction for multiple testing revealed 138 genes to be marginally significantly regulated due to MPH treatment, and one gene due to diagnosis. By qRT PCR we could confirm that GUCY1B3 expression was differential due to diagnosis. We verified chronic MPH treatment effects on the expression of ATXN1, HEY1, MAP3K8 and GLUT3 in controls as well as acute treatment effects on the expression of NAV2 and ATXN1 specifically in ADHD patients. CONCLUSIONS: Our preliminary results demonstrate MPH treatment differences in ADHD patients and healthy controls in a peripheral primary cell model. Our results need to be replicated in larger samples and also using patient-derived neuronal cell models to validate the contribution of those genes to the pathophysiology of ADHD and mode of action of MPH.
Published:
2015-04
Title:
Common Carotid Intima-Media Thickness Relates to Cardiovascular Events in Adults Aged <45 Years
Authors:
Eikendal, Anouk L.M.; Groenewegen, Karlijn A.; Anderson, Todd J.; Britton, Annie R.; Engström, Gunnar; Evans, Greg W.; de Graaf, Jacqueline; Grobbee, Diederick E.; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; Lonn, Eva M.; Lorenz, Matthias W.; Mathiesen, Ellisiv B.; Nijpels, Giel; Dekker, Jacqueline M.; Okazaki, Shuhei; O’Leary, Daniel H.; Polak, Joseph F.; Price, Jacqueline F.; Robertson, Christine; Rembold, Christopher M.; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T.; Sitzer, Matthias; Stehouwer, Coen D.A.; Hoefer, Imo E.; Peters, Sanne A.E.; Bots, Michiel L.; den Ruijter, Hester M.
Abstract:
Published:
2015-04
Title:
Diet-animal fractionation of nitrogen stable isotopes reflects the efficiency of nitrogen assimilation in ruminants
Authors:
Cantalapiedra-Hijar, G.; Ortigues-Marty, I.; Sepchat, B.; Agabriel, J.; Huneau, J. F.; Fouillet, H.
Abstract:
The natural abundance of 15N in animal proteins (delta15Nanimal) is greater than that in the diet consumed by the animals (delta15Ndiet), with a discrimination factor (DELTA15N = delta15Nanimal - delta15Ndiet) that is known to vary according to nutritional conditions. The objectives of the present study were to test the hypothesis that DELTA15N variations depend on the efficiency of nitrogen utilisation (ENU) in growing beef cattle, and to identify some of the physiological mechanisms responsible for this N isotopic fractionation in ruminants. Thus, we performed the regression of the DELTA15N of plasma proteins obtained from thirty-five finishing beef cattle fed standard and non-conventional diets against different feed efficiency indices, including ENU. We also performed the regression of the DELTA15N of different ruminant N pools (plasma and milk proteins, urine and faeces) against different splanchnic N fluxes obtained from multi-catheterised lactating dairy cows. The DELTA15N of plasma proteins was negatively correlated with feed efficiency indices in beef cattle, especially ENU (body protein gain/N intake) and efficiency of metabolisable protein (MP) utilisation (body protein gain/MP intake). Although DELTA15N obtained from different N pools in dairy cows were all negatively correlated with ENU, the highest correlation was found when DELTA15N was calculated from plasma proteins. DELTA15N showed no correlation with urea-N recycling or rumen NH3 absorption, but exhibited a strong correlation with liver urea synthesis and splanchnic amino acid metabolism, which points to a dominant role of splanchnic tissues in the present N isotopic fractionation study.
Published:
2015-04
Title:
Downregulation of PI3-K/Akt/PTEN pathway and activation of mitochondrial intrinsic apoptosis by Diclofenac and Curcumin in colon cancer
Authors:
Rana, Chandan; Piplani, Honit; Vaish, Vivek; Nehru, Bimla; Sanyal, S. N.
Abstract:
Phosphatidylinositol 3-kinase (PI3-K)/PTEN/Akt signaling is over activated in various tumors including colon cancer. Activation of this pathway regulates multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth that underlie the biology of a cancer cell. In the present study, the chemopreventive effects have been observed of Diclofenac, a preferential COX-2 inhibitory non-steroidal anti-inflammatory drugs, and Curcumin, a natural anti-inflammatory agent, in the early stage of colorectal carcinogenesis induced by 1,2-dimethylhydrazine dihydrochloride in rats. The tumor-promoting role of PI3-K/Akt/PTEN signal transduction pathway and its association with anti-apoptotic family of proteins are also observed. Both Diclofenac and Curcumin downregulated the PI3-K and Akt expression while promoting the apoptotic mechanism. Diclofenac and Curcumin administration significantly increased the expression of pro-apoptotic Bcl-2 family members (Bad and Bax) while decreasing the anti-apoptotic Bcl-2 protein. An up-regulation of cysteine protease family apoptosis executioner, such as caspase-3 and -9, is seen. Diclofenac and Curcumin inhibited the Bcl-2 protein by directly interacting at the active site by multiple hydrogen bonding, as also evident by negative glide score of Bcl-2. These drugs stimulated apoptosis by increasing reactive oxygen species (ROS) generation and simultaneously decreasing the mitochondrial membrane potential (ΔΨ M). Diclofenac and Curcumin showed anti-neoplastic effects by downregulating PI3-K/Akt/PTEN pathway, inducing apoptosis, increasing ROS generation, and decreasing ΔΨ M. The anti-neoplastic and apoptotic effects were found enhanced when both Diclofenac and Curcumin were administered together, rather than individually.
Published:
2015-04
Title:
Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects
Authors:
Hernandez-Alonso, P.; Salas-Salvado, J.; Baldrich-Mora, M.; Mallol, R.; Correig, X.; Bullo, M.
Abstract:
REGISTRATION NUMBER: This study is registered at www.clinicaltrials.gov as NCT01441921. Copyright © 2015 Elsevier B.V. All rights reserved.
Published:
2015-04
Title:
Effects of short- and long-term Mediterranean-based dietary treatment on plasma LC-QTOF/MS metabolic profiling of subjects with metabolic syndrome features: The Metabolic Syndrome Reduction in Navarra (RESMENA) randomized controlled trial
Authors:
Bondia-Pons, Isabel; Martinez, José Alfredo; de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Poutanen, Kaisa; Hanhineva, Kati; Zulet, Maria de los Ángeles
Abstract:
SCOPE: Adherence to the Mediterranean diet has been associated with a reduced risk of metabolic syndrome (MetS). Metabolomics approach may contribute to identify beneficial associations of metabolic changes affected by Mediterranean diet-based interventions with inflammatory and oxidative-stress markers related to the etiology and development of the MetS. METHODS AND RESULTS: Liquid chromatography coupled to quadrupole-time of flight-MS metabolic profiling was applied to plasma from a 6-month randomized intervention with two sequential periods, a 2-month nutritional-learning intervention period, and a 4-month self-control period, with two energy-restricted diets; the RESMENA diet (based on the Mediterranean dietary pattern) and the Control diet (based on the American Heart Association guidelines), in 72 subjects with a high BMI and at least two features of MetS. The major contributing biomarkers of each sequential period were lipids, mainly phospholipids and lysophospholipids. Dependency network analysis showed a different pattern of associations between metabolic changes and clinical variables after 2 and 6 month of intervention, with a highly interconnected network during the nutritional-learning intervention period of the study. CONCLUSION: The 2-month RESMENA diet produced significant changes in the plasma metabolic profile of subjects with MetS features. However, at the end of the 6-month study, most of the associations between metabolic and clinical variables disappeared; suggesting that adherence to healthy dietary habits had declined during the self-control period.
Published:
2015-04
Title:
Habitual physical activity and plasma metabolomic patterns distinguish individuals with low vs. high weight loss during controlled energy restriction
Authors:
Piccolo, Brian D; Keim, Nancy L; Fiehn, Oliver; Adams, Sean H; Van Loan, Marta D; Newman, John W
Abstract:
Background: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation.Objective: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity.Methods: Data were derived from a controlled feeding trial investigating the effect of 3-4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight-loss responders.Results: Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q(2) = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m(2); LR: 1.0 ± 0.6; HR: 3.3 ± 0.5, P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P
Published:
2015-04
Title:
High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice
Authors:
van der Heijden, Roel A.; Sheedfar, Fareeba; Morrison, Martine C.; Hommelberg, Pascal P. H.; Kor, Danny; Kloosterhuis, Niels J.; Gruben, Nanda; Youssef, Sameh A.; de Bruin, Alain; Hofker, Marten H.; Kleemann, Robert; Koonen, Debby P. Y.; Heeringa, Peter
Abstract:
Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains speculative. Thus, we aimed to elucidate the sequence of inflammatory events in adipose and hepatic tissues to determine their contribution to the development of metabolic inflammation and insulin resistance (IR) in diet-induced obesity. To confirm our hypothesis that adipose tissue (AT) inflammation is initiated prior to hepatic inflammation, C57BL/6J male mice were fed a low-fat diet (LFD; 10% kcal fat) or high-fat diet (HFD; 45% kcal fat) for either 24, 40 or 52 weeks. Lipid accumulation and inflammation was measured in AT and liver. Glucose tolerance was assessed and plasma levels of glucose, insulin, leptin and adiponectin were measured at various time points throughout the study. With HFD, C57BL/6j mice developed a progressive obese phenotype, accompanied by IR at 24 and 40 weeks of HFD, but IR was attenuated after 52 weeks of HFD. AT inflammation was present after 24 weeks of HFD, as indicated by the increased presence of crown-like structures and up-regulation of pro-inflammatory genes Tnf, Il1β, Mcp1 and F4/80. As hepatic inflammation was not detected until 40 weeks of HFD, we show that AT inflammation is established prior to the development of hepatic inflammation. Thus, AT inflammation is likely to have a greater contribution to the development of IR compared to hepatic inflammation.
Published:
2015-04
Title:
Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition
Authors:
Díaz-Rúa, Rubén; Keijer, Jaap; Caimari, Antoni; van Schothorst, Evert M.; Palou, Andreu; Oliver, Paula
Abstract:
Peripheral blood mononuclear cells (PBMCs) are accessible in humans, and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole-genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMCs allows for detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition.
Published:
2015-04
Title:
Plant-based, no-added-fat or American Heart Association diets: impact on cardiovascular risk in obese children with hypercholesterolemia and their parents
Authors:
Macknin, Michael; Kong, Tammie; Weier, Adam; Worley, Sarah; Tang, Anne S.; Alkhouri, Naim; Golubic, Mladen
Abstract:
OBJECTIVE: To perform a randomized trial to determine whether there is cardiovascular disease (CVD) risk reduction from a plant-based (PB), no-added-fat diet and the American Heart Association (AHA) diet in children. STUDY DESIGN: A 4-week (April 20, 2013 to May 18, 2013), prospective randomized trial was undertaken in a large, Midwestern hospital system's predominantly middle class outpatient pediatric practices. Thirty children (9-18 years of age) parent pairs with a last recorded child body mass index >95th percentile and child cholesterol >169 mg/dL were randomized to PB or AHA with weekly 2-hour classes of nutrition education. RESULTS: Children on PB had 9 and children on AHA had 4 statistically significant (P < .05) beneficial changes from baseline (mean decreases): body mass index z-score(PB) (-0.14), systolic blood pressure(PB) (-6.43 mm Hg), total cholesterol(PB) (-22.5 mg/dL), low-density lipoprotein(PB) (-13.14 mg/dL), high-sensitivity C-reactive protein(PB) (-2.09 mg/L), insulin(PB) (-5.42 uU/mL), myeloperoxidase(PB/AHA) (-75.34/69.23 pmol/L), mid-arm circumference(PB/AHA) (-2.02/-1.55 cm), weight(PB/AHA) (-3.05/-1.14 kg), and waist circumference(AHA) (-2.96 cm). Adults on PB and AHA had 7 and 2, respectively, statistically significant (P
Published:
2015-04
Title:
Possible adverse effects of frying with vegetable oils
Authors:
Dobarganes, Carmen; Márquez-Ruiz, Gloria
Abstract:
The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.
Published:
2015-04
Title:
Practicality of Intermittent Fasting in Humans and its Effect on Oxidative Stress and Genes Related to Aging and Metabolism
Authors:
Wegman, Martin P.; Guo, Michael H.; Bennion, Douglas M.; Shankar, Meena N.; Chrzanowski, Stephen M.; Goldberg, Leslie A.; Xu, Jinze; Williams, Tiffany A.; Lu, Xiaomin; Hsu, Stephen I.; Anton, Stephen D.; Leeuwenburgh, Christiaan; Brantly, Mark L.
Abstract:
Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods - IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.
Published:
2015-04
Title:
Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age
Authors:
Karlsson Videhult, Frida; Öhlund, Inger; Stenlund, Hans; Hernell, Olle; West, Christina
Abstract:
Purpose: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers. Methods: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting. Results: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers ( p > 0.05). Conclusion: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.
Published:
2015-04
Title:
SIRT3 mediates multi-tissue coupling for metabolic fuel switching
Authors:
Dittenhafer-Reed, Kristin E.; Richards, Alicia L.; Fan, Jing; Smallegan, Michael J.; Fotuhi Siahpirani, Alireza; Kemmerer, Zachary A.; Prolla, Tomas A.; Roy, Sushmita; Coon, Joshua J.; Denu, John M.
Abstract:
SIRT3 is a member of the Sirtuin family of NAD+-dependent deacylases and plays a critical role in metabolic regulation. Organism-wide SIRT3 loss manifests in metabolic alterations; however, the coordinating role of SIRT3 among metabolically distinct tissues is unknown. Using multi-tissue quantitative proteomics comparing fasted wild-type mice to mice lacking SIRT3, innovative bioinformatic analysis, and biochemical validation, we provide a comprehensive view of mitochondrial acetylation and SIRT3 function. We find SIRT3 regulates the acetyl-proteome in core mitochondrial processes common to brain, heart, kidney, liver, and skeletal muscle, but differentially regulates metabolic pathways in fuel-producing and fuel-utilizing tissues. We propose an additional maintenance function for SIRT3 in liver and kidney where SIRT3 expression is elevated to reduce the acetate load on mitochondrial proteins. We provide evidence that SIRT3 impacts ketone body utilization in the brain and reveal a pivotal role for SIRT3 in the coordination between tissues required for metabolic homeostasis.
Published:
2015-04
Title:
The evolution and functional impact of human deletion variants shared with archaic hominin genomes
Authors:
Lin, Yen-Lung; Pavlidis, Pavlos; Karakoc, Emre; Ajay, Jerry; Gokcumen, Omer
Abstract:
Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.
Published:
2015-04
Title:
The evolution and functional impact of human deletion variants shared with archaic hominin genomes
Authors:
Lin, Yen-Lung; Pavlidis, Pavlos; Karakoc, Emre; Ajay, Jerry; Gokcumen, Omer
Abstract:
Allele sharing between modern and archaic hominin genomes has been variously interpreted to have originated from ancestral genetic structure or through non-African introgression from archaic hominins. However, evolution of polymorphic human deletions that are shared with archaic hominin genomes has yet to be studied. We identified 427 polymorphic human deletions that are shared with archaic hominin genomes, approximately 87% of which originated before the Human-Neandertal divergence (ancient) and only approximately 9% of which have been introgressed from Neandertals (introgressed). Recurrence, incomplete lineage sorting between human and chimp lineages, and hominid-specific insertions constitute the remaining approximately 4% of allele sharing between humans and archaic hominins. We observed that ancient deletions correspond to more than 13% of all common (>5% allele frequency) deletion variation among modern humans. Our analyses indicate that the genomic landscapes of both ancient and introgressed deletion variants were primarily shaped by purifying selection, eliminating large and exonic variants. We found 17 exonic deletions that are shared with archaic hominin genomes, including those leading to three fusion transcripts. The affected genes are involved in metabolism of external and internal compounds, growth and sperm formation, as well as susceptibility to psoriasis and Crohn's disease. Our analyses suggest that these "exonic" deletion variants have evolved through different adaptive forces, including balancing and population-specific positive selection. Our findings reveal that genomic structural variants that are shared between humans and archaic hominin genomes are common among modern humans and can influence biomedically and evolutionarily important phenotypes.
Published:
2015-04
Title:
The pleiotropic effect of physical exercise on mitochondrial dynamics in aging skeletal muscle.
Authors:
Barbieri, Elena; Agostini, Deborah; Polidori, Emanuela; Potenza, Lucia; Guescini, Michele; Lucertini, Francesco; Annibalini, Giosuè; Stocchi, Laura; De Santi, Mauro; Stocchi, Vilberto
Abstract:
Decline in human muscle mass and strength (sarcopenia) is one of the principal hallmarks of the aging process. Regular physical exercise and training programs are certain powerful stimuli to attenuate the physiological skeletal muscle alterations occurring during aging and contribute to promote health and well-being. Although the series of events that led to these muscle adaptations are poorly understood, the mechanisms that regulate these processes involve the "quality" of skeletal muscle mitochondria. Aerobic/endurance exercise helps to maintain and improve cardiovascular fitness and respiratory function, whereas strength/resistance-exercise programs increase muscle strength, power development, and function. Due to the different effect of both exercises in improving mitochondrial content and quality, in terms of biogenesis, dynamics, turnover, and genotype, combined physical activity programs should be individually prescribed to maximize the antiaging effects of exercise.
Published:
2015-04
Title:
Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review
Authors:
Piccoli, G. B.; Clari, R.; Vigotti, F. N.; Leone, F.; Attini, R.; Cabiddu, G.; Mauro, G.; Castelluccia, N.; Colombi, N.; Capizzi, I.; Pani, A.; Todros, T.; Avagnina, P.
Abstract:
BACKGROUND: Although vegan-vegetarian diets are increasingly popular, no recent systematic reviews on vegan-vegetarian diets in pregnancy exist. OBJECTIVES: To review the literature on vegan-vegetarian diets and pregnancy outcomes. SEARCH STRATEGY: PubMed, Embase, and the Cochrane library were searched from inception to September 2013 for pregnancy and vegan or vegetarian Medical Subject Headings (MeSH) and free-text terms. SELECTION CRITERIA: Vegan or vegetarian diets in healthy pregnant women. We excluded case reports and papers analysing vegan-vegetarian diets in poverty and malnutrition. Searching, paper selection, and data extraction were performed in duplicate. DATA COLLECTION AND ANALYSIS: The high heterogeneity of the studies led to a narrative review. MAIN RESULTS: We obtained 262 full texts from 2329 references; 22 selected papers reporting maternal-fetal outcomes (13) and dietary deficiencies (nine) met the inclusion criteria. None of the studies reported an increase in severe adverse outcomes or in major malformations, except one report of increased hypospadias in infants of vegetarian mothers. Five studies reported vegetarian mothers had lower birthweight babies, yet two studies reported higher birthweights. The duration of pregnancy was available in six studies and was similar between vegan-vegetarians and omnivores. The nine heterogeneous studies on microelements and vitamins suggest vegan-vegetarian women may be at risk of vitamin B12 and iron deficiencies. AUTHOR'S CONCLUSIONS: The evidence on vegan-vegetarian diets in pregnancy is heterogeneous and scant. The lack of randomised studies prevents us from distinguishing the effects of diet from confounding factors. Within these limits, vegan-vegetarian diets may be considered safe in pregnancy, provided that attention is paid to vitamin and trace element requirements.
Published:
2015-04
Title:
Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review
Authors:
Piccoli, G. B.; Clari, R.; Vigotti, F. N.; Leone, F.; Attini, R.; Cabiddu, G.; Mauro, G.; Castelluccia, N.; Colombi, N.; Capizzi, I.; Pani, A.; Todros, T.; Avagnina, P.
Abstract:
BACKGROUND: Although vegan-vegetarian diets are increasingly popular, no recent systematic reviews on vegan-vegetarian diets in pregnancy exist. OBJECTIVES: To review the literature on vegan-vegetarian diets and pregnancy outcomes. SEARCH STRATEGY: PubMed, Embase, and the Cochrane library were searched from inception to September 2013 for pregnancy and vegan or vegetarian Medical Subject Headings (MeSH) and free-text terms. SELECTION CRITERIA: Vegan or vegetarian diets in healthy pregnant women. We excluded case reports and papers analysing vegan-vegetarian diets in poverty and malnutrition. Searching, paper selection, and data extraction were performed in duplicate. DATA COLLECTION AND ANALYSIS: The high heterogeneity of the studies led to a narrative review. MAIN RESULTS: We obtained 262 full texts from 2329 references; 22 selected papers reporting maternal-fetal outcomes (13) and dietary deficiencies (nine) met the inclusion criteria. None of the studies reported an increase in severe adverse outcomes or in major malformations, except one report of increased hypospadias in infants of vegetarian mothers. Five studies reported vegetarian mothers had lower birthweight babies, yet two studies reported higher birthweights. The duration of pregnancy was available in six studies and was similar between vegan-vegetarians and omnivores. The nine heterogeneous studies on microelements and vitamins suggest vegan-vegetarian women may be at risk of vitamin B12 and iron deficiencies. AUTHOR'S CONCLUSIONS: The evidence on vegan-vegetarian diets in pregnancy is heterogeneous and scant. The lack of randomised studies prevents us from distinguishing the effects of diet from confounding factors. Within these limits, vegan-vegetarian diets may be considered safe in pregnancy, provided that attention is paid to vitamin and trace element requirements.
Published:
2015-04
Title:
[Is emotional dysregulation a component of attention-deficit/hyperactivity disorder (ADHD)?]
Authors:
Villemonteix, T.; Purper-Ouakil, D.; Romo, L.
Abstract:
INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents. It is characterized by age-inappropriate inattention/impulsiveness and/or hyperactivity symptoms. ADHD shows a high comorbidity with oppositional defiant disorder (ODD), a disorder that features symptoms of emotional lability. Due to this comorbidity, emotional lability was long considered a secondary consequence of ADHD, which could arise under the influence of environmental factors such as inefficient parenting practices, as part of an ODD diagnosis. In this model of heterotypic continuity, emotional lability was considered not to play any causal role regarding ADHD symptomatology. LITERATURE FINDINGS: As opposed to this view, it is now well established that a large number of children with ADHD and without any comorbid disorder exhibit symptoms of emotional lability. Furthermore, recent studies have found that negative emotionality accounts for significant unique variance in ADHD symptom severity, along with motor-perceptual and executive function deficits. Barkley proposed that ADHD is characterized by deficits of executive functions, and that a deficiency in the executive control of emotions is a necessary component of ADHD. According to this theory, the extent to which an individual with ADHD displays a deficiency in behavioral inhibition is the extent to which he or she will automatically display an equivalent degree of deficiency in emotional inhibition. However, not all children with ADHD exhibit symptoms of emotional lability, and studies have found that the association between emotional lability and ADHD was not mediated by executive function or motivational deficits. Task-based and resting state neuroimaging studies have disclosed an altered effective connectivity between regions dedicated to emotional regulation in children with ADHD when compared to typically developing children, notably between the amygdala, the prefrontal cortex, the hippocampus and the ventral striatum. Morphological alterations of the amygdala have also been reported in previous structural studies in children with ADHD. DISCUSSION: Emotional lability can result from different neurobiological mechanisms. In particular, bottom-up and top-down processes can be opposed. Bottom-up related emotional dysregulation involves an increased emotional reactivity, and is thought to be linked to the automatic evaluative activity of the amygdala. Top-down mechanisms are associated with the regulation of such activity, and rely on a prefrontal network including the lateral prefrontal cortex, the anterior cingulate cortex and the orbitofrontal cortex. Since various neuropsychological impairments and alterations in multiple brain networks have been implicated in the etiology of ADHD, contemporary models emphasize its neuropsychological heterogeneity. It is therefore likely that some but not all children with ADHD will exhibit neurobiological alterations in circuits dedicated to emotional regulation, possibly at different levels. Future research will have to identify the different causal pathways and to decide whether emotional lability represents a criterion to subtype ADHD diagnoses. CONCLUSION: Emotional dysregulation is now known to play a causal role regarding ADHD symptomatology. Along with executive functioning, reaction time variability and potentially delay aversion, emotional dysregulation should therefore be included in future theoretical models of ADHD, as well as in clinical practice when identifying the major impairments in this diagnostic group and when deciding therapeutic strategies.
Published:
2015-04
Title:
[Oxygen-dependent energy deficit as related to the problems of ontogenetic development disorders and human sociobiological adaptation (theoretical and applied aspects)]
Authors:
Ilyukhina, V. A.; Kataeva, G. V.; Korotkov, A. D.; Chernysheva, E. M.
Abstract:
The review states and argues theoretical propositions on the pathogenetic role of pre- and perinatal hypoxic-ischemic brain damage in the formation of sustained oxygen-dependent energy deficit underlying in further ontogenesis the following neurobiological abnormalities: a) a decline in the level of health and compensatory-adaptive capacities of the organism, b) disorders of the psycho-speech development and adaptive behavior in children, c) early development of neuropsychic diseases, g) addition of other types of brain energy metabolism (including glucose metabolism) disorders in chronic polyetiologic diseases young and middle-aged individuals. We highlight and theoretically substantiate the integrated physiological parameters of the oxygen-dependent energy deficit types. We address the features of abnormalities in neuroreflectory and neurohumora regulatory mechanisms of the wakefulness level and its vegetative and hemodynamic provision in different types of energy deficit in children with DSMD, ADHD and school maladjustment. The use of the state-of-the-art neuroimaging techniques significantly increased the possibility of the disintegration of regulatory processes and cognitive functions in children with psycho-speech delays and in a wide range of chronic polyetiologic diseases.
Published:
2015-04
Title:
A century of cholesterol and coronaries: from plaques to genes to statins. [Review]
Authors:
Goldstein, Joseph L.; Brown, Michael S.
Abstract:
One-fourth of all deaths in industrialized countries result from coronary heart disease. A century of research has revealed the essential causative agent: cholesterol-carrying low-density lipoprotein (LDL). LDL is controlled by specific receptors (LDLRs) in liver that remove it from blood. Mutations that eliminate LDLRs raise LDL and cause heart attacks in childhood, whereas mutations that raise LDLRs reduce LDL and diminish heart attacks. If we are to eliminate coronary disease, lowering LDL should be the primary goal. Effective means to achieve this goal are currently available. The key questions are: who to treat, when to treat, and how long to treat. Copyright © 2015 Elsevier Inc. All rights reserved.
Published:
2015-03
Title:
Alcohol withdrawal delirium manifested by manic symptoms in an elderly patient: Manic symptoms in withdrawal delirium
Authors:
Chan, Hung-Yu; Lee, Kuan-I
Abstract:
Alcohol withdrawal syndrome is a commonly seen problem in psychiatric practice. Alcohol withdrawal delirium is associated with significant morbidity and mortality. Withdrawal symptoms usually include tremulousness, psychotic and perceptual symptoms, seizures, and consciousness disturbance. Herein, we report a case involving a 63-year-old man who had alcohol withdrawal delirium that was manifested mainly by manic symptoms.
Published:
2015-03
Title:
Antibody against α-gliadin 33-mer peptide: Is the key initiating factor for development of multiple sclerosis during gluten sensitivity?
Authors:
Mokarizadeh, Aram; Esmaeili, Parisa; Soraya, Hamid; Hassanzadeh, Kambiz; Jalili, Ali; Abdi, Mohammad; Faryabi, Mohammad Reza
Abstract:
Published:
2015-03
Title:
Apiaceous vegetable consumption decreases PhIP-induced DNA adducts and increases methylated PhIP metabolites in the urine metabolome in rats
Authors:
Kim, Jae Kyeom; Gallaher, Daniel D; Chen, Chi; Yao, Dan; Trudo, Sabrina P
Abstract:
Background: Heterocyclic aromatic amines, such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are carcinogenic compounds produced during heating of protein-containing foods. Apiaceous vegetables inhibit PhIP-activating enzymes, whereas cruciferous vegetables induce both PhIP-activating and -detoxifying enzymes.Objective: We investigated the effects of these vegetables, either alone or combined, on PhIP metabolism and colonic DNA adduct formation in rats.Methods: Male Wistar rats were fed cruciferous vegetables (21%, wt:wt), apiaceous vegetables (21%, wt:wt), or a combination of both vegetables (10.5% wt:wt of each). Negative and positive control groups were fed an AIN-93G diet. After 6 d, all groups received an intraperitoneal injection of PhIP (10 mg · kg body weight(-1)) except for the negative control group, which received only vehicle. Urine was collected for 24 h after the injection for LC-tandem mass spectrometry metabolomic analyses. On day 7, rats were killed and tissues processed.Results: Compared with the positive control, cruciferous vegetables increased the activity of hepatic PhIP-activating enzymes [39.5% and 45.1% for cytochrome P450 (CYP) 1A1 (P = 0.0006) and CYP1A2 (P
Published:
2015-03
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