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Title:
Developmental Programming of Obesity and Diabetes in Mouse, Monkey, and Man in 2018: Where Are We Headed?
Authors:
Friedman, Jacob E.
Abstract:
Childhood obesity and its comorbidities continue to accelerate across the globe. Two-thirds of pregnant women are obese/overweight, as are 20% of preschoolers. Gestational diabetes mellitus (GDM) is escalating, affecting up to 1 in 5 pregnant women. The field of developmental origins of health and disease has begun to move beyond associations to potential causal mechanisms for developmental programming. Evidence across species compellingly demonstrates that maternal obesity, diabetes, and Western-style diets create a long-lasting signature on multiple systems, including infant stem cells, the early immune system, and gut microbiota. Such exposures accelerate adipogenesis, disrupt mitochondrial metabolism, and impair energy sensing, affecting neurodevelopment, liver, pancreas, and skeletal muscle. Attempts to prevent developmental programming have met with very limited success. A challenging level of complexity is involved in how the host genome, metabolome, and microbiome throughout pregnancy and lactation increase the offspring's risk of metabolic diseases across the life span. Considerable gaps in knowledge include the timing of exposure(s) and permanence or plasticity of the response, encompassing effects from both maternal and paternal dysmetabolism. Basic, translational, and human intervention studies targeting pathways that connect diet, microbiota, and metabolism in mothers with obesity/GDM and their infants are a critical unmet need and present new challenges for disease prevention in the next generation.
Published:
2018-11
Title:
Fasting and cancer: molecular mechanisms and clinical application
Authors:
Nencioni, Alessio; Caffa, Irene; Cortellino, Salvatore; Longo, Valter D.
Abstract:
This Opinion discusses the potential of fasting and fasting-mimicking diets to help overcome toxicities induced by anticancer therapy. The differential response of normal and cancer cells undergoing starvation is argued to make normal cells less sensitive to therapy-induced toxicity, while cancer cells become more sensitive to therapy-induced cell death.
Published:
2018-11
Title:
Hydroxyhydroquinone impairs fat utilization in mice by reducing nitric oxide availability
Authors:
Ishida, Keiko; Misawa, Koichi; Yamamoto, Masaki; Shimotoyodome, Akira
Abstract:
Habitual consumption of chlorogenic acid compounds (CGAs) from coffee increases fat catabolism and reduces body fat; however, the contribution of roasted coffee remains unclear. Hydroxyhydroquinone (HHQ) impairs the vasodilatory and antihypertensive effects of CGAs by reducing nitric oxide (NO) bioavailability. Since HHQ also reduces fat catabolism, we hypothesized that HHQ does so by decreasing NO availability. Therefore, we investigated the effect of HHQ on energy metabolism in KKAy mice. In HHQ-treated mice, fat oxidation was significantly low and dose-dependent, serum and urinary hydrogen peroxide were high, and plasma NO metabolites and S-nitrosylated liver proteins were low. In HHQ-treated mouse hepatocytes, the palmitate-induced increase in cellular oxygen consumption was negatively affected, and HHQ or L-NAME reduced cellular fatty acid utilization. In conclusion, HHQ can impair fat utilization by reducing NO availability in mice. Protein S-nitrosylation reduction in liver cells after HHQ consumption may be associated with impaired fatty acid oxidation.
Published:
2018-11
Title:
PKM2 promotes reductive glutamine metabolism
Authors:
Liu, Miao; Wang, Yuanyuan; Ruan, Yuxia; Bai, Changsen; Qiu, Li; Cui, Yanfen; Ying, Guoguang; Li, Binghui
Abstract:
Objective: Pyruvate kinases M (PKM), including the PKM1 and PKM2 isoforms, are critical factors in glucose metabolism. PKM2 promotes aerobic glycolysis, a phenomenon known as " the Warburg effect". The purpose of this study was to identify the roles of PKM2 in regulating cellular metabolism. Methods: The CRISPR/Cas9 system was used to generate the PKM-knockout cell model to evaluate the role of PKM in cellular metabolism. Lactate levels were measured by the Vitros LAC slide method on an autoanalyzer and glucose levels were measured by the autoanalyzer AU5800. The metabolism of 13C6-glucose or 13C5-glutamine was evaluated by liquid chromatography/mass spectrometry analyses. The effects of PKM on tumor growth were detected in vivo in a tumor-bearing mouse model. Results: We found that both PKM1 and PKM2 enabled aerobic glycolysis, but PKM2 converted glucose to lactate much more efficiently than PKM1. As a result, PKM2 reduced glucose levels reserved for intracellular utilization, particularly for the production of citrate, and thus increased the α-ketoglutarate/citrate ratio to promote the generation of glutamine-derived acetyl-coenzyme A through the reductive pathway. Furthermore, reductive glutamine metabolism facilitated cell proliferation under hypoxia conditions, which supports in vivo tumor growth. In addition, PKM-deletion induced a reverse Warburg effect in tumor-associated stromal cells. Conclusions: PKM2 plays a critical role in promoting reductive glutamine metabolism and maintaining proton homeostasis. This study is helpful to increase the understanding of the physiological role of PKM2 in cancer cells.
Published:
2018-11
Title:
Strongly heated carbohydrate-rich food is an overlooked problem in cancer risk evaluation
Authors:
Abramsson-Zetterberg, Lilianne
Abstract:
A cascade of compounds is produced when foodstuffs are heated at high temperatures but only a few of these compounds have been identified and quantified. In this study data are evaluated regarding differences in the micronucleus frequency of human erythrocytes (fMNs) in peripheral blood (a known biomarker of genotoxicity) in individuals that consumed either high- or low-heated food during a 4-day period. Concomitantly, acrylamide (aa) levels were measured in the food that the participants consumed. The obtained fMNs in this human study are compared with the fMNs in mice after comparable exposure levels of pure aa. The results of this comparison showed several hundred times higher fMNs in humans compared with mice. With an assumed linear correlation between an increased genotoxic effect and cancer, our data suggest that aa only represents a fraction of all carcinogenic compounds produced in heated carbohydrate-rich food. Consequently, our daily intake of carbohydrate-rich food heated at high temperatures might be responsible for one-fifth of the rate of the total cancer risk. ONE SENTENCE SUMMARY: A biomarker of genotoxicity indicates the risk of cancer to be some hundred-fold greater in heated carbohydrate-rich food than the risk calculated from animal studies on pure acrylamide.
Published:
2018-11
Title:
Study on the levels of glycosylated lipoprotein in patients with coronary artery atherosclerosis
Authors:
Kawasoe, Shin; Ide, Kazuki; Usui, Tomoko; Kubozono, Takuro; Yoshifuku, Shiro; Miyahara, Hironori; Maenohara, Shigeho; Ohishi, Mitsuru; Kawakami, Koji; Gjuladin-Hellon, Teuta; Davies, Ian G; Penson, Peter; Amiri Baghbadorani, Raziyeh; Lamarche, Benoît; Tchernof, André; Mauriège, Pascale; Cantin, Bernard; Dagenais, Gilles R.; Lupien, Paul J.; Després, Jean Pierre; Ravnskov, Uffe; de Lorgeril, Michel; Diamond, David M.; Hama, Rokuro; Hamazaki, Tomohito; Hammarskjöld, Björn; Hynes, Niamh; Kendrick, Malcolm; Langsjoen, Peter H.; Mascitelli, Luca; McCully, Kilmer S.; Okuyama, Harumi; Rosch, Paul J.; Schersten, Tore; Sultan, Sherif; Sundberg, Ralf; Zimmermann, Robert; Panzenböck, Ute; Wintersperger, Andrea; Levak-Frank, Sanja; Graier, Wolfgang; Glatter, Otto; Fritz, Gerhard; Kostner, Gerhard M.; Zechner, Rudolf; Calvo, Carlos; Talussot, Corinne; Ponsin, Gabriel; Berthézène, Francois; Luo, Wei; He, Yong; Ding, Fei; Nie, Xin; Li, Xiao Ling; Song, Hao Lan; Li, Gui Xing
Abstract:
BACKGROUND The main risk factors for atherosclerosis patients are not fully explicated. The aim of this study was to analyze the levels of blood lipid and glycosylated lipoprotein in patients with coronary artery atherosclerosis and healthy individuals and to study the relationship between the glycosylated lipoprotein and atherosclerosis. METHODS The study involved 200 patients diagnosed with myocardial infarction caused by coronary atherosclerosis as case group and 230 healthy individuals as control group. We analyzed and contrasted the levels of blood lipid and glycosylated lipoprotein between the different groups. In addition, we investigated the correlation between glycosylated low-density lipoprotein (G-LDL) and glucose levels. RESULTS There is no statistical difference between the level of TG in case group and control group. The level of CHOL, HDL-C, and LDL-C in case group is significantly lower than that in control group (3.90 [3.23, 4.42] vs 5.16 [4.86, 5.77] [mmol/L]; 1.09 [0.83, 1.38] vs 1.46 [1.15, 1.80] [mmol/L]; 2.22 [1.68, 2.81] vs 2.95 [2.60, 3.27] [mmol/L]) (P \textless 0.05). The level of GLU, HbA1c, G-HDL, and G-LDL in case group is significantly higher than that in control group (7.10 [5.68, 9.27] vs 4.84 [4.68, 5.07] [mmol/L]; 6.8 [6.3, 7.4] vs 5.9 [5.6, 6.1] [%]; 30.08 [25.04, 40.17] vs 22.95 [18.14, 27.06] [ng/mL], 6.26 [4.95, 7.50] vs 3.61 [2.66, 5.15] [ng/mL]) (p \textless 0.05). The level of G-LDL in patients with coronary atherosclerosis was relevant with the level of GLU and HbA1c (r = 0.625, 0.706, P \textless 0.05), and there was no relevance with LDL-C (r = 0.331, P \textgreater 0.05). CONCLUSION Hyperlipidemia is not an important cause of coronary atherosclerosis. High glucose levels and glycosylated lipoprotein are of high importance in the development and progression of coronary atherosclerosis.
Published:
2018-11
Title:
Telomere length as a biomarker of accelerated aging: is it influenced by dietary intake?
Authors:
Freitas-Simoes, Tania-Marisa; Ros, Emilio; Sala-Vila, Aleix
Abstract:
Purpose Of Review: There is increasing interest in exploring whether age-related diseases can be prevented by dietary means through nutrients or food bioactives, whole foods, or specific dietary patterns. Because of the slow nature of the aging process, biomarkers such as telomere length are helpful for this purpose. Here we update the developments in the area during the last 2 years.Recent Findings: Most data stem from epidemiologic studies, often cross-sectional in design. Recent articles strengthened the link between consumption of sugar-sweetened beverages and telomere shortening, whereas a novel association between telomere length and drinking coffee has been uncovered. Controversy on meat consumption and telomere length persists, mostly because of the presumed different effects of total meat and processed meat. In general terms, increasing consumption of antioxidant-rich plant foods relates to maintained telomere length. Feeding intervention trials with outcomes on telomere length are few and thus far have contributed little to further knowledge on this topic.Summary: Epidemiologic studies provide support for the putative effects of diet components on telomere length and on the aging process in general. Dietary associations with telomere length should be confirmed with adequately powered randomized controlled trials.
Published:
2018-11
Title:
The Effect of On-Line Hemodiafiltration, Vegetarian Diet, and Urine Volume on Advanced Glycosylation End Products Measured by Changes in Skin Auto-Fluorescence
Authors:
Nongnuch, Arkom; Davenport, Andrew
Abstract:
Increasing urea clearance by hemodialysis (HD) has not improved patient survival. Hemodiafiltration (HDF) has been reported to reduce cardiovascular mortality. HDF increases middle sized solute clearances. Advanced glycosylation end products (AGEs) are associated with increased cardiovascular mortality. We wished to determine whether HDF reduces AGEs. Skin auto-fluorescence (SAF) measures circulating AGEs deposited in the skin. We compared SAF measurements 12 months apart in high flux HD and HDF patients. At enrollment SAF was not different (HD 3.34 ± 0.71 vs. HDF 3.48 ± 1.05 AU). At seven months after completion of SAF measurement, one hemodiafiltration center returned to hemodialysis, and one hemodialysis center converted to hemodiafiltration. In the 66 patients treated solely by high flux HD, SAF increased (3.36 ± 0.71 to 3.82 ± 0.88 AU, P 0.9). SAF increased in 34 patients switching from HDF to high flux HD (3.52 ± 0.94 vs. 3.88 ± 1.05, P 0.3). On multivariate analysis, SAF was associated with older age (β coefficient 0.013, P = 0.002), prescription of insulin (β 0.29, P = 0.016), lanthanum (β 0.36, P = 0.004), and warfarin (β 0.62, P = 0.012), whereas vegetarian diet and > 250 mL/day residual urine volume were negatively associated with SAF (β -0.58, P = 0.002 and β -0.26, P = 0.033 respectively). Residual urine output and vegetarian diet were associated with lower AGE deposition. Whereas SAF increased over time in patients treated with high flux HD, there was no statistical change in SAF in those exclusively treated by HDF.
Published:
2018-11
Title:
Breaking the rules: Phylogeny, not life history, explains dental eruption sequence in primates
Authors:
Monson, Tesla A.; Hlusko, Leslea J.
Abstract:
Objectives: Although a great deal is known about the biology of tooth development and eruption, there remains disagreement about the factors driving the evolution of dental eruption sequence. We assessed postcanine eruption sequence across a large sample of primates to test two hypotheses: (1) Dental eruption sequence is significantly correlated with life history and body size variables that capture postnatal growth and longevity (Schultz's rule), and (2) Dental eruption sequence is conserved phylogenetically. Materials and methods: We assessed postcanine dental eruption sequence for 194 individuals representing 21 primate genera spanning eight families. With the inclusion of an additional 29 primate genera from the literature, this is the most comprehensive report on dental eruption sequence in primates to date. We used a series of phylogenetic analyses to statistically compare dental eruption sequence to life history and body size and test for phylogenetic signal in these traits. Results: Dental eruption sequence is conserved phylogenetically in primates, and body and brain size are both significantly associated with dental eruption sequence. Ancestral state reconstruction supports the hypothesis that the third molar erupted before one or more of the premolars in the ancestor of primates, and derived clades within primates evolved an eruption sequence in which the third molar erupts after the premolars. Discussion: Schultz's rule, as it is currently written and applied, is not supported by this extended data set. Our results demonstrate that dental eruption sequence is a far better predictor of phylogeny and will likely prove useful in phylogenetic hypotheses about relationships between extinct and extant mammalian taxa. The evolution of dental eruption sequence is likely driven by factors that significantly influence body size and mandibular symphyseal fusion.
Published:
2018-10
Title:
Employing proteomics to understand the effects of nutritional intervention in cancer treatment
Authors:
Schroll, Monica M.; Hummon, Amanda B.
Abstract:
Lifestyle optimizations are implementable changes that can have an impact on health and disease. Nutrition is a lifestyle optimization that has been shown to be of great importance in cancer initiation, progression, and metastasis. Dozens of clinical trials are currently in progress that focus on the nutritional modifications that cancer patients can make prior to and during medical care that increase the efficacy of treatment. In this review, we discuss various nutritional inventions for cancer patients and the analytical approaches to characterize the downstream molecular effects. We first begin by briefly explaining the many different forms of nutritional intervention currently being used in cancer treatment as well as their motivating biology. The forms of nutrient modulation described in this review include calorie restriction, the different practices of fasting, and carbohydrate restriction. The review then shifts to explain how proteomics is used to determine biomarkers of cancer and how it can be utilized in the future to determine the metabolic phenotype of a tumor, and inform physicians if nutritional intervention should be recommended for a cancer patient. Nutrigenomics aims to understand the relationship of nutrients and gene expression and can be used to understand the downstream molecular effects of nutrition restriction, partially through proteomic analysis. Proteomics is just beginning to be used as cancer diagnostic and predictive tools. However, these approaches have not been used to their full potential to understand nutritional intervention in cancer. Graphical abstract ᅟ.
Published:
2018-10
Title:
Human Breast Milk NMR Metabolomic Profile across Specific Geographical Locations and Its Association with the Milk Microbiota
Authors:
Gómez-Gallego, Carlos; Morales, Jose Manuel; Monleón, Daniel; du Toit, Elloise; Kumar, Himanshu; Linderborg, Kaisa M.; Zhang, Yumei; Yang, Baoru; Isolauri, Erika; Salminen, Seppo; Collado, Maria Carmen
Abstract:
The composition of human breast milk is highly variable, and it can be influenced by genetics, diet, lifestyle, and other environmental factors. This study aimed to investigate the impact of geographical location and mode of delivery on the nuclear magnetic resonance spectroscopy (NMR) metabolic profile of breast milk and its relationship with the milk microbiome. Human milk metabolic and microbiota profiles were determined using NMR and 16S rRNA gene sequencing, respectively, in 79 healthy women from Finland, Spain, South Africa, and China. Up to 68 metabolites, including amino acids, oligosaccharides, and fatty acid-associated metabolites, were identified in the milk NMR spectra. The metabolite profiles showed significant differences between geographical locations, with significant differences (p
Published:
2018-10
Title:
Impact of Agaricus bisporus Mushroom Consumption on Gut Health Markers in Healthy Adults
Authors:
Hess, Julie; Wang, Qi; Gould, Trevor; Slavin, Joanne
Abstract:
Eating Agaricus bisporus mushrooms may impact gut health, because they contain known prebiotics. This study assessed mushroom consumption compared to meat on gastrointestinal tolerance, short chain fatty acid (SCFA) production, laxation, and fecal microbiota. A randomized open-label crossover study was conducted in healthy adults (n = 32) consuming protein-matched amounts of mushrooms or meat twice daily for ten days. Breath hydrogen measures were taken on day one, and gastrointestinal tolerance was evaluated throughout treatments. Fecal sample collection was completed days 6-10, and samples were assessed for bacterial composition, SCFA concentrations, weight, pH, and consistency. There were no differences in breath hydrogen, stool frequency, consistency, fecal pH, or SCFA concentrations between the two diets. The mushroom diet led to greater overall gastrointestinal symptoms than the meat diet on days one and two. The mushroom-rich diet resulted in higher average stool weight (p = 0.002) and a different fecal microbiota composition compared to the meat diet, with greater abundance of Bacteroidetes (p = 0.0002) and lower abundance of Firmicutes (p = 0.0009). The increase in stool weight and presence of undigested mushrooms in stool suggests that mushroom consumption may impact laxation in healthy adults. Additional research is needed to interpret the health implications of fecal microbiota shifts with mushroom feeding.
Published:
2018-10
Title:
Insulin resistance disrupts cell integrity, mitochondrial function and inflammatory signaling in lymphatic endothelium
Authors:
Lee, Yang; Chakraborty, Sanjukta; Meininger, Cynthia J.; Muthuchamy, Mariappan
Abstract:
Objective: Lymphatic vessel dysfunction and increased lymph leakage have been directly associated with several metabolic diseases. However, the underlying cellular mechanisms causing lymphatic dysfunction have not been determined. Aberrant insulin signaling affects the metabolic function of cells, and consequently impairs tissue function. We hypothesized that insulin resistance in lymphatic endothelial cells (LECs) decreases eNOS activity, disrupts barrier integrity increases permeability, and activates mitochondrial dysfunction and pro-inflammatory signaling pathways. Methods: LECs were treated with insulin and/or glucose to determine the mechanisms leading to insulin resistance. Results: Acute insulin treatment increased eNOS phosphorylation and NO production in LECs via activation of the PI3K/Akt signaling pathway. Prolonged hyperglycemia and hyperinsulinemia induced insulin resistance in LECs. Insulin resistant LECs produced less NO due to a decrease in eNOS phosphorylation and showed a significant decrease in impedance across an LEC monolayer that was associated with disruption in the adherence junctional proteins. Additionally, insulin resistance in LECs impaired mitochondrial function by decreasing basal-, maximal-, and ATP-linked-oxygen consumption rates and activated NF-κB nuclear translocation coupled with increased pro-inflammatory signaling. Conclusion: Our data provide the first evidence that insulin resistance disrupts endothelial barrier integrity, decreases eNOS phosphorylation and mitochondrial function, and activates inflammation in LECs.
Published:
2018-10
Title:
LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature
Authors:
Ravnskov, Uffe; de Lorgeril, Michel; Diamond, David M.; Hama, Rokuro; Hamazaki, Tomohito; Hammarskjöld, Björn; Hynes, Niamh; Kendrick, Malcolm; Langsjoen, Peter H.; Mascitelli, Luca; McCully, Kilmer S.; Okuyama, Harumi; Rosch, Paul J.; Schersten, Tore; Sultan, Sherif; Sundberg, Ralf
Abstract:
INTRODUCTION: For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit. Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis. Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.
Published:
2018-10
Title:
Metabolomic profile of insulin resistance in patients with multiple sclerosis is associated to the severity of the disease
Authors:
Ruiz-Argüelles, Alejandro; Méndez-Huerta, Mariana A.; Lozano, Claudia D.; Ruiz-Argüelles, Guillermo J.
Abstract:
BACKGROUND: Dysglycemia and adiposity have been related to disability in patients with multiple sclerosis. The objective of this work was to determine the prevalence and characteristics of insulin resistance in patients with multiple sclerosis using the metabolomics Quantose score. METHODS: A total of 64 patients were accrued in the study. A blood sample was drawn to estimate the Quantose score, which is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. RESULTS: Insulin resistance was documented in 33 out of 64 patients and it was found in association with the degree of disability and the time from diagnosis. Patients with the secondary progressive form of the disease showed the highest prevalence. CONCLUSION: Insulin resistance is frequent in patients with multiple sclerosis and might contribute to metabolic complications and general disability. Early markers of dysglycemia should be sought for in these patients to avoid additional deterioration of their quality of life.
Published:
2018-10
Title:
Silencing of PYGB suppresses growth and promotes the apoptosis of prostate cancer cells via the NF-κB/Nrf2 signaling pathway
Authors:
Wang, Zhen; Han, Gang; Liu, Qinghong; Zhang, Wenyuan; Wang, Jinshan
Abstract:
Brain-type glycogen phosphorylase (PYGB) is an enzyme that metabolizes glycogen, whose function is to provide energy for an organism in an emergency state. The present study purposed to investigate the role and mechanism of PYGB silencing on the growth and apoptosis of prostate cancer cells. A cell counting kit-8 assay and flow cytometry were performed to determine the cell viability, apoptosis and reactive oxygen species (ROS) content, respectively. Colorimetry was performed to analyze the activity of caspase-3. Western blotting and reverse transcription-quantitative polymerase chain reaction were used to evaluate the associated mRNA and protein expression levels. The results revealed that PYGB was upregulated in prostate cancer tissues and was associated with disease progression. In addition, PYGB silencing suppressed the cell viability of PC3 cells. PYGB silencing promoted apoptosis of PC3 cells via the regulation of the expression levels of cleaved-poly (adenosine diphosphate-ribose) polymerase, cleaved-caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein. PYGB silencing increased the ROS content in PC3 cells, and affected nuclear factor (NF)-κB/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathways in PC3 cells. In conclusion, PYGB silencing suppressed the growth and promoted the apoptosis of prostate cancer cells by affecting the NF-κB/Nrf2 signaling pathway. The present study provided evidence that may lead to the development of a potential therapeutic strategy for prostate cancer.
Published:
2018-10
Title:
So What Comes First: The Obesity or the Insulin Resistance? And Which Is More Important?
Authors:
Noakes, Timothy David
Abstract:
Unless it is religion, there is no field of human thought in which sentiment and prejudice take the place of sound judgment and logical thinking so completely as in dietetics (1) (p. 191). Once upon a time, humans were for the most part lean and, apart from susceptibility to infections and trauma, perhaps healthier than today (2). The most long-lived in those populations may also have lived for as long as do modern elderly. All were also less likely to die from the “chronic diseases of lifestyle” (2) that have become increasingly prevalent in the past century. There are two contrasting explanations for why so many modern humans suffer from that constellation of chronic diseases—obesity, hypertension, type 2 diabetes mellitus, coronary heart disease, dementia, and cancer—that were much less common even as recently as the 1970s (3). The first implies that our current predicament is largely of our individual making. According to this reasoning, over the past 50 years humans have simply become, well, just progressively lazier and more voracious. The resulting sloth and gluttony means that we now willfully eat too many calories, leading to an obesity pandemic that began in the early 1980s (4). As our obesity increases, storage of triglyceride in the abdominal organs, especially the liver, causes the key associated complications of obesity—specifically insulin resistance (5), hypertension (6), nonalcoholic fatty liver disease (7), and atherogenic dyslipidemia (8)—all of which explain our current epidemic rates of coronary heart disease (9), dementia (10), and even perhaps cancer (11). The less-than-subtle inference is that it is our own bad “lifestyle” choices that trigger the corpulence that causes all these chronic medical conditions (“of lifestyle”). This model fits nicely with a paternalistic model of medicine. When our medical advice and management fail, ultimately it is the \ldots
Published:
2018-10
Title:
Subversion of Systemic Glucose Metabolism as a Mechanism to Support the Growth of Leukemia Cells
Authors:
Ye, Haobin; Adane, Biniam; Khan, Nabilah; Alexeev, Erica; Nusbacher, Nichole; Minhajuddin, Mohammad; Stevens, Brett M.; Winters, Amanda C.; Lin, Xi; Ashton, John M.; Purev, Enkhtsetseg; Xing, Lianping; Pollyea, Daniel A.; Lozupone, Catherine A.; Serkova, Natalie J.; Colgan, Sean P.; Jordan, Craig T.
Abstract:
From an organismal perspective, cancer cell populations can be considered analogous to parasites that compete with the host for essential systemic resources such as glucose. Here, we employed leukemia models and human leukemia samples to document a form of adaptive homeostasis, where malignant cells alter systemic physiology through impairment of both host insulin sensitivity and insulin secretion to provide tumors with increased glucose. Mechanistically, tumor cells induce high-level production of IGFBP1 from adipose tissue to mediate insulin sensitivity. Further, leukemia-induced gut dysbiosis, serotonin loss, and incretin inactivation combine to suppress insulin secretion. Importantly, attenuated disease progression and prolonged survival are achieved through disruption of the leukemia-induced adaptive homeostasis. Our studies provide a paradigm for systemic management of leukemic disease.
Published:
2018-10
Title:
The Consumption of Beef Burgers Prepared with Wine Grape Pomace Flour Improves Fasting Glucose, Plasma Antioxidant Levels, and Oxidative Damage Markers in Humans: A Controlled Trial
Authors:
Urquiaga, Inés; Troncoso, Danitza; Mackenna, Maria José; Urzúa, Catalina; Pérez, Druso; Dicenta, Sara; de la Cerda, Paula María; Amigo, Ludwig; Carreño, Juan Carlos; Echeverría, Guadalupe; Rigotti, Attilio
Abstract:
Wine grape pomace flour (WGPF) is a fruit byproduct that is high in fiber and antioxidants. We tested whether WGPF consumption could affect blood biochemical parameters, including oxidative stress biomarkers. In a three-month intervention study, 27 male volunteers, each with some components of metabolic syndrome, consumed a beef burger supplemented with 7% WGPF containing 3.5% of fiber and 1.2 mg gallic equivalents (GE)/g of polyphenols (WGPF-burger), daily, during the first month. The volunteers consumed no burgers in the second month, and one control-burger daily in the third month. At baseline and after these periods, we evaluated the metabolic syndrome components, plasma antioxidant status (i.e., 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH), vitamin E, vitamin C), and oxidative damage markers (i.e., advanced oxidation protein products (AOPPs), oxidized low-density lipoproteins (oxLDLs), malondialdehyde (MDA)). The WGPF-burger intake significantly reduced glycemia and homeostatic model assessment-based measurement of insulin resistance. Vitamin C increased and decreased during the consumption of the WGPF-burger and control-burger, respectively. The WGPF-burger intake significantly decreased AOPP and oxLDL levels. Vitamin E and MDA levels showed no significant changes. In conclusion, the consumption of beef burgers prepared with WGPF improved fasting glucose and insulin resistance, plasma antioxidant levels, and oxidative damage markers. Therefore, this functional ingredient has potential as a dietary supplement to manage chronic disease risk in humans.
Published:
2018-10
Title:
The Lifestyle History: A Neglected But Essential Component of the Medical History
Authors:
Houlden, Robyn L.; Yen, Hope H.; Mirrahimi, Arash
Abstract:
There is increased recognition that lifestyle factors, including nutrition, physical activity, emotional well-being and stress management, tobacco use, alcohol consumption, and sleep habits, are major determinants of health. There is a need to teach practicing physicians, medical trainees, and other health care providers how to perform a "lifestyle history." This article proposes 13 screening questions physicians should consider exploring with patients. It provides the rationale and scientific evidence supporting each question and includes key lifestyle counseling points for clinicians to consider.
Published:
2018-10
Title:
A Dietary Intervention to Lower Serum Levels of IGF-I in BRCA Mutation Carriers
Authors:
Pasanisi, Patrizia; Bruno, Eleonora; Venturelli, Elisabetta; Morelli, Daniele; Oliverio, Andreina; Baldassari, Ivan; Rovera, Francesca; Iula, Giovanna; Taborelli, Monica; Peissel, Bernard; Azzollini, Jacopo; Manoukian, Siranoush
Abstract:
Background: Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might influence the penetrance of BRCA gene mutation. In a demonstration project on BRCA mutation carriers we tested the effect of the 'Mediterranean diet', with moderate protein restriction, on serum levels of IGF-I and IRm. Methods: BRCA mutation carriers, with or without breast cancer, aged 18–70 years and without metastases were eligible. After the baseline examinations, women were randomized to an active dietary intervention or to a control group. The intervention group attended six full days of life-style intervention activities (cookery classes followed by lunch, sessions of walking for 45 min and nutritional conferences) over the next six months. Results: 213 BRCA mutation carriers completed the six-month study. Women in the intervention group (110) showed major changes in all the parameters under study. They significantly lost weight (p
Published:
2018-09
Title:
Anti-Inflammatory and Pro-Inflammatory Adipokine Profiles in Children on Vegetarian and Omnivorous Diets
Authors:
Ambroszkiewicz, Jadwiga; Chelchowska, Magdalena; Rowicka, Grazyna; Klemarczyk, Witold; Strucinska, Malgorzata; Gajewska, Joanna
Abstract:
Adipose tissue is a highly active endocrine organ that secrets many pro-inflammatory as well anti-inflammatory adipokines. The aim of the study was to assess serum adipokine profile in prepubertal vegetarian and omnivorous children. Sixty-two children on a vegetarian diet and fifty-five children on an omnivorous diet, aged 5 to 10 years, were studied. Dietary assessment was performed using a nutritional software program. Body composition was measured by dual-energy X-ray absorptiometry. Serum concentrations of adipokines: leptin, soluble leptin receptor (sOB-R), adiponectin (total and high molecular weight), resistin, visfatin, vaspin, and omentin were determined by immunoenzymatic assays. Both studied groups of children were comparable in terms of age, weight, height, body mass index, and body composition. Vegetarians had a lower (p = 0.017) leptin/sOB-R ratio and lower serum concentrations of resistin (p = 0.051), compared with omnivores. Average levels of other adipokines did not differ between both groups of children. However, we observed significantly higher ratios of anti-inflammatory to pro-inflammatory adipokines: adiponectin/leptin 0.70 (0.37-0.93) vs 0.39 (0.28-0.74), p = 0.005, and omentin/leptin 0.40 (0.23-0.83) vs. 0.33 (0.15-0.48), p = 0.011 in vegetarians compared with omnivores. A well-planned vegetarian diet might beneficially affect the adipokine profile and inflammatory status expressed by the ratios of anti-inflammatory to pro-inflammatory adipokines in prepubertal children.
Published:
2018-09
Title:
Association between habitual dietary and lifestyle behaviours and skin autofluorescence (SAF), a marker of tissue accumulation of advanced glycation endproducts (AGEs), in healthy adults
Authors:
Kellow, Nicole J.; Coughlan, Melinda T.; Reid, Christopher M.
Abstract:
Purpose: Advanced glycation endproducts (AGEs) are produced endogenously and also enter the body during the consumption of AGEs present in heat-processed food. It is unknown whether AGEs of dietary origin accumulate within the body of healthy individuals. AGEs can deposit within skin tissue long-term by crosslinking extracellular matrix proteins. The fluorescent nature of many AGEs enables their detection within the skin by non-invasively measuring skin autofluorescence (SAF). This study aimed to identify habitual dietary and lifestyle behaviours cross-sectionally associated with SAF in an adult population sample.Methods: 251 Healthy adult volunteers completed validated food frequency and physical activity questionnaires. Waist circumference, BMI, blood pressure and blood glucose was also measured. SAF was measured using an AGE Reader.Results: Significant positive correlations were found between SAF and chronological age (r = 0.63, P < 0.001), waist circumference (r = 0.28, P < 0.01), body weight (r = 0.24, P < 0.05), BMI (r = 0.23, P < 0.05) and consumption of meat and meat products (r = 0.22, P < 0.05). A negative correlation was found between SAF and cereal consumption (r = −0.21, P < 0.05). Cigarette smokers also had a significantly higher SAF than non-smokers (2.4 vs 2.0 U, P
Published:
2018-09
Title:
Challenges in the Diagnosis of Magnesium Status
Authors:
Workinger, Jayme L.; Doyle, Robert P.; Bortz, Jonathan
Abstract:
Magnesium is a critical mineral in the human body and is involved in ~80% of known metabolic functions. It is currently estimated that 60% of adults do not achieve the average dietary intake (ADI) and 45% of Americans are magnesium deficient, a condition ...
Published:
2018-09
Title:
Fasting or starving? Measurement of blood ketone levels in 100 fasted elective and emergency adult surgical patients at an Australian tertiary hospital.
Authors:
Burstal, R J; Reilly, J R; Burstal, B
Abstract:
Prolonged fasting leads to a shift from carbohydrate to fat as the primary energy source, resulting in the production of ketones such as beta-hydroxybutyrate. Hyperketonaemia and ketoacidosis have been observed in young children fasting for surgery. The aim of this study was to investigate ketonaemia in adults fasted for surgery. One hundred non-diabetic adults presenting for elective or emergency surgery were assessed for the presence of hyperketonaemia (beta-hydroxybutyrate levels more than 1 mmol/l), and the relationship between beta-hydroxybutyrate, blood glucose and fasting duration was investigated. Three of 100 patients demonstrated hyperketonaemia, one of whom had ingested a ketogenic supplement the evening prior to surgery. No patient demonstrated beta-hydroxybutyrate levels suggestive of ketoacidosis (above 3 mmol/l). No relationship between fasting duration and ketone or glucose levels was observed. We found no evidence that prolonged preoperative fasting led to beta-hydroxybutyrate levels consistent with ketoacidosis.
Published:
2018-09
Title:
Food groups and intermediate disease markers: a systematic review and network meta-analysis of randomized trials
Authors:
Schwingshackl, Lukas; Hoffmann, Georg; Iqbal, Khalid; Schwedhelm, Carolina; Boeing, Heiner
Abstract:
Background: In previous meta-analyses of prospective observational studies, we investigated the association between food groups and risk of chronic disease. Objective: The aim of the present network meta-analysis (NMA) was to assess the effects of these food groups on intermediate-disease markers across randomized intervention trials. Design: Literature searches were performed until January 2018. The following inclusion criteria were defined a priori: 1) randomized trial (≥4 wk duration) comparing ≥2 of the following food groups: refined grains, whole grains, nuts, legumes, fruits and vegetables, eggs, dairy, fish, red meat, and sugar-sweetened beverages (SSBs); 2) LDL cholesterol and triacylglycerol (TG) were defined as primary outcomes; total cholesterol, HDL cholesterol, fasting glucose, glycated hemoglobin, homeostasis model assessment insulin resistance, systolic and diastolic blood pressure, and C-reactive protein were defined as secondary outcomes. For each outcome, a random NMA was performed, and for the ranking, the surface under the cumulative ranking curves (SUCRA) was determined. Results: A total of 66 randomized trials (86 reports) comparing 10 food groups and enrolling 3595 participants was identified. Nuts were ranked as the best food group at reducing LDL cholesterol (SUCRA: 93%), followed by legumes (85%) and whole grains (70%). For reducing TG, fish (97%) was ranked best, followed by nuts (78%) and red meat (72%). However, these findings are limited by the low quality of the evidence. When combining all 10 outcomes, the highest SUCRA values were found for nuts (66%), legumes (62%), and whole grains (62%), whereas SSBs performed worst (29%). Conclusion: The present NMA provides evidence that increased intake of nuts, legumes, and whole grains is more effective at improving metabolic health than other food groups. For the credibility of diet-disease relations, high-quality randomized trials focusing on well-established intermediate-disease markers could play an important role.
Published:
2018-09
Title:
Glucosinolate turnover in Brassicales species to an oxazolidin-2-one, formed via the 2-thione and without formation of thioamide
Authors:
Agerbirk, Niels; Matthes, Annemarie; Erthmann, Pernille Ø; Ugolini, Luisa; Cinti, Susanna; Lazaridi, Eleni; Nuzillard, Jean-Marc; Müller, Caroline; Bak, Søren; Rollin, Patrick; Lazzeri, Luca
Abstract:
Glucosinolates are found in plants of the order Brassicales and hydrolyzed to different breakdown products, particularly after tissue damage. In Barbarea vulgaris R.Br. (Brassicaceae), the dominant glucosinolate in the investigated "G-type" is glucobarbarin, (S)-2-hydroxy-2-phenylethylglucosinolate. Formation of the nitrile from glucobarbarin was observed in vitro, while a previously suggested thioamide (synonym thionamide) was not confirmed. Resedine (5-phenyl-1,3-oxazolidin-2-one) was detected after glucobarbarin hydrolysis in crushed B. vulgaris leaves and siliques, but not in intact parts. The abundance increased for several hours after completion of hydrolysis. The corresponding 1,3-oxazolidine-2-thione (OAT), with the common name barbarin, was also formed, and appeared to be the precursor of resedine. Addition of each of two non-endogenous OATs, (S)-5-ethyl-5-methylOAT and (R)-5-vinylOAT (R-goitrin), to a leaf homogenate resulted in formation of the corresponding 1,3-oxazolidin-2-ones (OAOs), confirming the metabolic connection of OAT to OAO. Formation of OAOs was inhibited by prior brief heating of the homogenate, suggesting enzyme involvement. We suggest the conversion of OATs to OAOs to be catalyzed by an enzyme ("oxazolidinethionase") responsible for turnover of OAT formed in intact plants. Resedine had been reported as an alkaloid from another species - Reseda luteola L. (Resedaceae) - naturally containing the glucosinolate glucobarbarin. However, resedine was not detected in intact R. luteola plants, but formed after tissue damage. The formation of resedine in two families suggests a broad distribution of putative OATases in the Brassicales; potentially involved in glucosinolate turnover that needs myrosinase activity as the committed step. In agreement with the proposed function of OATase, several candidate genes for myrosinases in glucosinolate turnover in intact plants were discovered in the B. vulgaris genome. We also suggest that biotechnological conversion of OATs to OAOs might improve the nutritional value of Brassicales protein. HPLC-MS/MS methods for detection of these glucobarbarin products are described.
Published:
2018-09
Title:
Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss
Authors:
Mani, Kartik; Javaheri, Ali; Diwan, Abhinav
Abstract:
Adaptive responses that counter starvation have evolved over millennia to permit organismal survival, including changes at the level of individual organelles, cells, tissues, and organ systems. In the past century, a shift has occurred away from disease caused by insufficient nutrient supply toward overnutrition, leading to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden of these diseases has spurred interest in fasting strategies that harness physiological responses to starvation, thus limiting tissue injury during metabolic stress. Insights gained from animal and human studies suggest that intermittent fasting and chronic caloric restriction extend lifespan, decrease risk factors for cardiometabolic and inflammatory disease, limit tissue injury during myocardial stress, and activate a cardioprotective metabolic program. Acute fasting activates autophagy, an intricately orchestrated lysosomal degradative process that sequesters cellular constituents for degradation, and is critical for cardiac homeostasis during fasting. Lysosomes are dynamic cellular organelles that function as incinerators to permit autophagy, as well as degradation of extracellular material internalized by endocytosis, macropinocytosis, and phagocytosis. The last decade has witnessed an explosion of knowledge that has shaped our understanding of lysosomes as central regulators of cellular metabolism and the fasting response. Intriguingly, lysosomes also store nutrients for release during starvation; and function as a nutrient sensing organelle to couple activation of mammalian target of rapamycin to nutrient availability. This article reviews the evidence for how the lysosome, in the guise of a janitor, may be the "undercover boss" directing cellular processes for beneficial effects of intermittent fasting and restoring homeostasis during feast and famine. © 2018 American Physiological Society. Compr Physiol 8:1639-1667, 2018.
Published:
2018-09
Title:
Methylmalonic Acid Levels and their Relation with Cobalamin Supplementation in Spanish Vegetarians
Authors:
Gallego-Narbón, Angélica; Zapatera, Belén; Álvarez, Inmaculada; Vaquero, M. Pilar
Abstract:
Cobalamin deficiency represents a health issue for vegetarians, especially vegans, if supplements are not consumed. Vitamin B12 serum levels, traditionally used to assess the vitamin B12 status, can be normal under functional deficiency conditions. In this regard, methylmalonic acid (MMA) has proven to be a more specific marker to detect subclinical vitamin B12 deficiency. In this study, we present for the first time the cobalamin status of Spanish vegetarians using both vitamin B12 and MMA markers, and the effects of the plant-based diet and the intake of vitamin B12 supplements. Healthy adults were recruited (n = 103, 52% vegans). Dietary preferences and use of supplements were assessed by questionnaires and serum samples were collected and stored. Vitamin B12 was measured by chemiluminiscence and MMA by liquid chromatography tandem mass spectrometry (LC-MS/MS) using solid phase extraction for sample preparation. Obtained values, median (IQR), were: vitamin B12, 278.9 (160.2) pmol/l and MMA, 140.2 (78.9) nmol/l. No significant differences between lacto-ovo vegetarians and vegans were observed. Considering these two markers, 10% of the participants were mild vitamin B12 deficient. Supplementation (75% of the participants) was associated with higher vitamin B12 (p
Published:
2018-09
Title:
Plant versus animal based diets and insulin resistance, prediabetes and type 2 diabetes: the Rotterdam Study
Authors:
Chen, Zhangling; Zuurmond, Maria Geertruida; van der Schaft, Niels; Nano, Jana; Wijnhoven, Hanneke Anna Hendrikje; Ikram, Mohammad Arfan; Franco, Oscar Horacio; Voortman, Trudy
Abstract:
Vegan or vegetarian diets have been suggested to reduce type 2 diabetes (T2D) risk. However, not much is known on whether variation in the degree of having a plant-based versus animal-based diet may be beneficial for prevention of T2D. We aimed to investigate whether level of adherence to a diet high in plant-based foods and low in animal-based foods is associated with insulin resistance, prediabetes, and T2D. Our analysis included 6798 participants (62.7 ± 7.8 years) from the Rotterdam Study (RS), a prospective population-based cohort in the Netherlands. Dietary intake data were collected with food-frequency questionnaires at baseline of three sub-cohorts of RS (RS-I-1: 1989-1993, RS-II-1: 2000-2001, RS-III-1: 2006-2008). We constructed a continuous plant-based dietary index (range 0-92) assessing adherence to a plant-based versus animal-based diet. Insulin resistance at baseline and follow-up was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Prediabetes and T2D were collected from general practitioners' records, pharmacies' databases, and follow-up examinations in our research center until 2012. We used multivariable linear mixed models to examine association of the index with longitudinal HOMA-IR, and multivariable Cox proportional-hazards regression models to examine associations of the index with risk of prediabetes and T2D. During median 5.7, and 7.3 years of follow-up, we documented 928 prediabetes cases and 642 T2D cases. After adjusting for sociodemographic and lifestyle factors, a higher score on the plant-based dietary index was associated with lower insulin resistance (per 10 units higher score: β = -0.09; 95% CI: - 0.10; - 0.08), lower prediabetes risk (HR = 0.89; 95% CI: 0.81; 0.98), and lower T2D risk [HR = 0.82 (0.73; 0.92)]. After additional adjustment for BMI, associations attenuated and remained statistically significant for longitudinal insulin resistance [β = -0.05 (- 0.06; - 0.04)] and T2D risk [HR = 0.87 (0.79; 0.99)], but no longer for prediabetes risk [HR = 0.93 (0.85; 1.03)]. In conclusion, a more plant-based and less animal-based diet may lower risk of insulin resistance, prediabetes and T2D. These findings strengthen recent dietary recommendations to adopt a more plant-based diet.Clinical Trial Registry number and website NTR6831, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831 .
Published:
2018-09
Title:
The role of diet in the aetiopathogenesis of inflammatory bowel disease
Authors:
Khalili, Hamed; Chan, Simon S. M.; Lochhead, Paul; Ananthakrishnan, Ashwin N.; Hart, Andrew R.; Chan, Andrew T.
Abstract:
Crohn’s disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene–environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions.
Published:
2018-09
Title:
The role of miniaturization in the evolution of the mammalian jaw and middle ear
Authors:
Lautenschlager, Stephan; Gill, Pamela G.; Luo, Zhe-Xi; Fagan, Michael J.; Rayfield, Emily J.
Abstract:
The evolution of the mammalian jaw is one of the most important innovations in vertebrate history, and underpins the exceptional radiation and diversification of mammals over the last 220 million years1,2. In particular, the transformation of the mandible into a single tooth-bearing bone and the emergence of a novel jaw joint—while incorporating some of the ancestral jaw bones into the mammalian middle ear—is often cited as a classic example of the repurposing of morphological structures3,4. Although it is remarkably well-documented in the fossil record, the evolution of the mammalian jaw still poses the paradox of how the bones of the ancestral jaw joint could function both as a joint hinge for powerful load-bearing mastication and as a mandibular middle ear that was delicate enough for hearing. Here we use digital reconstructions, computational modelling and biomechanical analyses to demonstrate that the miniaturization of the early mammalian jaw was the primary driver for the transformation of the jaw joint. We show that there is no evidence for a concurrent reduction in jaw-joint stress and increase in bite force in key non-mammaliaform taxa in the cynodont–mammaliaform transition, as previously thought5,6,7,8. Although a shift in the recruitment of the jaw musculature occurred during the evolution of modern mammals, the optimization of mandibular function to increase bite force while reducing joint loads did not occur until after the emergence of the neomorphic mammalian jaw joint. This suggests that miniaturization provided a selective regime for the evolution of the mammalian jaw joint, followed by the integration of the postdentary bones into the mammalian middle ear.
Published:
2018-09
Title:
Worldwide Variation in Human Milk Metabolome: Indicators of Breast Physiology and Maternal Lifestyle?
Authors:
Investigators, InVIVO LactoActive Study; Gay, Melvin C. L.; Geddes, Donna T.; Munblit, Daniel; Kozyrskyj, Anita L.; Koleva, Petya T.; Slupsky, Carolyn M.; Toit, Elloise du; Eggesbo, Merete; Johnson, Christine C.; Wegienka, Ganesa; Shimojo, Naoki; Campbell, Dianne E.; Prescott, Susan L.
Abstract:
Human milk provides essential substrates for the optimal growth and development of a breastfed infant. Besides providing nutrients to the infant, human milk also contains metabolites which form an intricate system between maternal lifestyle, such as the mother's diet and the gut microbiome, and infant outcomes. This study investigates the variation of these human milk metabolites from five different countries. Human milk samples (n = 109) were collected one month postpartum from Australia, Japan, the USA, Norway, and South Africa and were analyzed by nuclear magnetic resonance. The partial least squares discriminant analysis (PLS-DA) showed separation between either maternal countries of origin or ethnicities. Variation between countries in concentration of metabolites, such as 2-oxoglutarate, creatine, and glutamine, in human milk, between countries, could provide insights into problems, such as mastitis and/or impaired functions of the mammary glands. Several important markers of milk production, such as lactose, betaine, creatine, glutamate, and glutamine, showed good correlation between each metabolite. This work highlights the importance of milk metabolites with respect to maternal lifestyle and the environment, and also provides the framework for future breastfeeding and microbiome studies in a global context.
Published:
2018-09
Title:
Chronic non-communicable disease risks presented by lipid oxidation products in fried foods
Authors:
Grootveld, Martin; Percival, Benita C.; Grootveld, Kerry L.
Abstract:
LOPs detectable in fried foods are both cytotoxic and genotoxic, and currently a substantial proportion of the human population regularly consumes such toxins in Western diets.
Published:
2018-08
Title:
Consumption of a defined, plant-based diet reduces lipoprotein(a), inflammation, and other atherogenic lipoproteins and particles within 4 weeks
Authors:
Najjar, Rami S.; Moore, Carolyn E.; Montgomery, Baxter D.
Abstract:
BACKGROUND: Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein and is minimally effected by lifestyle changes. While some drugs can reduce Lp(a), diet has not consistently shown definitive reduction of this biomarker. The effect of consuming a plant-based diet on serum Lp(a) concentrations have not been previously evaluated. HYPOTHESIS: Consumption of a defined, plant-based for 4 weeks reduces Lp(a). METHODS: Secondary analysis of a previous trial was conducted, in which overweight and obese individuals (n = 31) with low-density lipoprotein cholesterol concentrations >100 mg/dL consumed a defined, plant-based diet for 4 weeks. Baseline and 4-week labs were collected. Data were analyzed using a paired samples t-test. RESULTS: Significant reductions were observed for serum Lp(a) (-32.0 ± 52.3 nmol/L, P = 0.003), apolipoprotein B (-13.2 ± 18.3 mg/dL, P < 0.0005), low-density lipoprotein (LDL) particles (-304.8 ± 363.0 nmol/L, P < 0.0005) and small-dense LDL cholesterol (-10.0 ± 9.2 mg/dL, P
Published:
2018-08
Title:
Dietary cholesterol does not break your heart but kills your liver
Authors:
Püschel, Gerhard P.; Henkel, Janin
Abstract:
It is increasingly accepted that dietary cholesterol has a much lower impact on the progression of cardiovascular disease than previously assumed. However, both animal experiments and human studies seem to support the view that dietary cholesterol may contribute to the transition from benign steatosis to the potentially fatal non-alcoholic steatohepatitis. Cholesterol esters and cholesterol accumulate in the hepatocyte and impair its function. This leads to oxidative stress and endoplasmic reticulum stress triggering the release of pro-inflammatory cytokines and rendering the hepatocyte more susceptible to apoptotic or necrotic cell death. Kupffer cells group around dying hepatocytes and phagocytose the hepatocyte debris and lipids. In addition, they are exposed to lipid peroxidation products released from hepatocytes. Kupffer cells, thus activated, release pro-inflammatory, chemotactic and profibrotic cytokines that promote inflammation and fibrosis. Therefore, dietary cholesterol may be harmful to the liver, in particular when administered in combination with polyunsaturated fatty acids that favor lipid peroxidation.
Published:
2018-08
Title:
Improving compliance in adults with epilepsy on a modified Atkins diet: A randomized trial
Authors:
McDonald, Tanya J.W.; Henry-Barron, Bobbie J.; Felton, Elizabeth A.; Gutierrez, Erie G.; Barnett, Joanne; Fisher, Rebecca; Lwin, MonYi; Jan, Amanda; Vizthum, Diane; Kossoff, Eric H.; Cervenka, Mackenzie C.
Abstract:
Published:
2018-08
Title:
Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results
Authors:
Kaysen, George A.; Ye, Xiaoling; Raimann, Jochen G.; Wang, Yuedong; Topping, Alice; Usvyat, Len A.; Stuard, Stefano; Canaud, Bernard; van der Sande, Frank M.; Kooman, Jeroen P.; Kotanko, Peter; on behalf of the Monitoring Dialysis Outcomes (MONDO) Initiative
Abstract:
Published:
2018-08
Title:
Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial
Authors:
Phillips, Matthew C. L.; Murtagh, Deborah K. J.; Gilbertson, Linda J.; Asztely, Fredrik J. S.; Lynch, Christopher D. P.
Abstract:
BACKGROUND: Preliminary evidence suggests that diet manipulation may influence motor and nonmotor symptoms in PD, but conflict exists regarding the ideal fat to carbohydrate ratio. OBJECTIVES: We designed a pilot randomized, controlled trial to compare the plausibility, safety, and efficacy of a low-fat, high-carbohydrate diet versus a ketogenic diet in a hospital clinic of PD patients. METHODS: We developed a protocol to support PD patients in a diet study and randomly assigned patients to a low-fat or ketogenic diet. Primary outcomes were within- and between-group changes in MDS-UPDRS Parts 1 to 4 over 8 weeks. RESULTS: We randomized 47 patients, of which 44 commenced the diets and 38 completed the study (86% completion rate for patients commencing the diets). The ketogenic diet group maintained physiological ketosis. Both groups significantly decreased their MDS-UPDRS scores, but the ketogenic group decreased more in Part 1 (-4.58 ± 2.17 points, representing a 41% improvement in baseline Part 1 scores) compared to the low-fat group (-0.99 ± 3.63 points, representing an 11% improvement) (P
Published:
2018-08
Title:
Nutritional Metabolomics: Postprandial Response of Meals Relating to Vegan, Lacto-Ovo Vegetarian, and Omnivore Diets
Authors:
Rådjursöga, Millie; Lindqvist, Helen M.; Pedersen, Anders; Karlsson, B. Göran; Malmodin, Daniel; Ellegård, Lars; Winkvist, Anna
Abstract:
Metabolomics provide an unbiased tool for exploring the modulation of the human metabolome in response to food intake. This study applied metabolomics to capture the postprandial metabolic response to breakfast meals corresponding to vegan (VE), lacto ovo-vegetarian (LOV), and omnivore (OM) diets. In a cross over design 32 healthy volunteers (16 men and 16 females) consumed breakfast meals in a randomized order during three consecutive days. Fasting and 3 h postprandial serum samples were collected and then subjected to metabolite profiling using 1H-nuclear magnetic resonance (NMR) spectroscopy. Changes in concentration of identified and discriminating metabolites, between fasting and postprandial state, were compared across meals. Betaine, choline, and creatine displayed higher concentration in the OM breakfast, while 3-hydroxyisobutyrate, carnitine, proline, and tyrosine showed an increase for the LOV and unidentified free fatty acids displayed a higher concentration after the VE breakfast. Using 1H NMR metabolomics it was possible to detect and distinguish the metabolic response of three different breakfast meals corresponding to vegan, lacto-ovo vegetarian, and omnivore diets in serum.
Published:
2018-08
Title:
Residue Depletion of Florfenicol and Florfenicol Amine in Broiler Chicken Claws and a Comparison of Their Concentrations in Edible Tissues Using LC-MS/MS
Authors:
Pokrant, Ekaterina; Riquelme, Ricardo; Maddaleno, Aldo; San Martin, Betty; Cornejo, Javiera
Abstract:
Antimicrobial residues might persist in products and by-products destined for human or animal consumption. Studies exploring the depletion behavior of florfenicol residues in broiler chicken claws are scarce, even though claws can enter the food chain directly or indirectly. Hence, this study intended to assess the concentrations of florfenicol (FF) and florfenicol amine (FFA)-its active metabolite-in chicken claws from birds that were treated with a therapeutic dose of florfenicol. Furthermore, concentrations of these analytes in this matrix were compared with their concentrations in edible tissues at each sampling point. A group of 70 broiler chickens were raised under controlled conditions and used to assess residue depletion. Sampling points were on days 5, 10, 20, 25, 30, 35, and 40 after ceasing treatment, thus extending beyond the withdrawal period established for muscle tissue (30 days). Analytes were extracted using HPLC-grade water and acetone, and dichloromethane was used for the clean-up stage. Liquid chromatography coupled to mass spectroscopy detection (LC-MS/MS) was used to detect and quantify the analytes. The analytical methodology developed in this study was validated in-house and based on the recommendations described in the Commission Decision 2002/657/EC from the European Union. Analyte concentrations were calculated by linear regression analysis of calibration curves that were fortified using an internal standard of chloramphenicol-d5 (CAF-d5). The depletion time of FF and FFA was set at 74 days in claws, based on a 95% confidence level and using the limit of detection (LOD) as the cut-off point. Our findings show that FF and FFA can be found in chicken claws at higher concentrations than in muscle and liver samples at each sampling point.
Published:
2018-08
Title:
The expanding role of Ketogenic diets in adult neurological disorders
Authors:
McDonald, Tanya J.W.; Cervenka, Mackenzie C.
Abstract:
The current review highlights the evidence supporting the use of ketogenic diet therapies in the management of adult epilepsy, adult malignant glioma and Alzheimer's disease. An overview of the scientific literature, both preclinical and clinical, in each area is presented and management strategies for addressing adverse effects and compliance are discussed.
Published:
2018-08
Title:
Β-Hydroxybutyrate Elicits Favorable Mitochondrial Changes in Skeletal Muscle
Authors:
Parker, Brian A.; Walton, Chase M.; Carr, Sheryl T.; Andrus, Jacob L.; Cheung, Eric C.K.; Duplisea, Michael J.; Wilson, Esther K.; Draney, Carrie; Lathen, Daniel R.; Kenner, Kyle B.; Thomson, David M.; Tessem, Jeffery S.; Bikman, Benjamin T.
Abstract:
The clinical benefit of ketosis has historically and almost exclusively centered on neurological conditions, lending insight into how ketones alter mitochondrial function in neurons. However, there is a gap in our understanding of how ketones influence mitochondria within skeletal muscle cells. The purpose of this study was to elucidate the specific effects of β-hydroxybutyrate (β-HB) on muscle cell mitochondrial physiology. In addition to increased cell viability, murine myotubes displayed beneficial mitochondrial changes evident in reduced H2O2 emission and less mitochondrial fission, which may be a result of a β-HB-induced reduction in ceramides. Furthermore, muscle from rats in sustained ketosis similarly produced less H2O2 despite an increase in mitochondrial respiration and no apparent change in mitochondrial quantity. In sum, these results indicate a general improvement in muscle cell mitochondrial function when β-HB is provided as a fuel.
Published:
2018-08
Title:
A stromal cell population that inhibits adipogenesis in mammalian fat depots
Authors:
Schwalie, Petra C.; Dong, Hua; Zachara, Magda; Russeil, Julie; Alpern, Daniel; Akchiche, Nassila; Caprara, Christian; Sun, Wenfei; Schlaudraff, Kai-Uwe; Soldati, Gianni; Wolfrum, Christian; Deplancke, Bart
Abstract:
Adipocyte development and differentiation have an important role in the aetiology of obesity and its co-morbidities1,2. Although multiple studies have investigated the adipogenic stem and precursor cells that give rise to mature adipocytes3–14, our understanding of their in vivo origin and properties is incomplete2,15,16. This is partially due to the highly heterogeneous and unstructured nature of adipose tissue depots17, which has proven difficult to molecularly dissect using classical approaches such as fluorescence-activated cell sorting and Cre–lox lines based on candidate marker genes16,18. Here, using the resolving power of single-cell transcriptomics19 in a mouse model, we reveal distinct subpopulations of adipose stem and precursor cells in the stromal vascular fraction of subcutaneous adipose tissue. We identify one of these subpopulations as CD142+ adipogenesis-regulatory cells, which can suppress adipocyte formation in vivo and in vitro in a paracrine manner. We show that adipogenesis-regulatory cells are refractory to adipogenesis and that they are functionally conserved in humans. Our findings point to a potentially critical role for adipogenesis-regulatory cells in modulating adipose tissue plasticity, which is linked to metabolic control, differential insulin sensitivity and type 2 diabetes.
Published:
2018-07
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