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Title:
Mechanisms underlying fat pad remodeling induced by fasting: role of PAF receptor.
Authors:
Lacerda, Débora Romualdo; Soares, Danusa Dias; Costa, Kátia Anunciação; Nunes-Silva, Albena; Rodrigues, Débora Fernandes; Sabino, Josiana Lopes; Silveira, Ana Letícia Malheiros; Pinho, Vanessa; Vieira, Érica Leandro Marciano; Menezes, Gustavo Batista; Antunes, Maísa Mota; Teixeira, Mauro Martins; Ferreira, Adaliene Versiani Matos
Abstract:
OBJECTIVES Fasting has long been practiced for political and religious reasons and to lose weight. However, biological responses during fasting have yet to be fully understood. Previous studies have shown that cytokines may control fat pad expansion, at least in part, owing to the induction of lipolysis. Indeed, we have previously shown that mice with a lower inflammatory response, such as platelet-activating factor receptor knockout mice (PAFR-/-), are prone to gain weight and adiposity. The aims of this study were to determine whether adipose tissue becomes inflamed after fasting and to evaluate whether the PAF signaling is a factor in the fat loss induced by fasting. METHODS Wild-type (WT) and PAFR-/- mice were fasted for 24 h. Adiposity, leukocyte recruitment, and cytokine levels were evaluated. Multiple comparisons were performed using two-way analysis of variance and post hoc Fisher exact test. RESULTS After fasting, male WT mice showed lower adiposity (P \textless 0.001), higher recruitment of immune cells (P \textless 0.001), and increased cytokine levels (P \textless 0.05) in adipose tissue. Although WT mice lost ∼79% of their adipose tissue mass, PAFR-/- mice lost only 36%. Additionally, PAFR-/- mice did not show enhanced cytokine and chemokine levels after fasting (P \textgreater 0.05). CONCLUSION Despite low-grade inflammation being associated with metabolic syndrome, at least in part, the inflammatory milieu is also important to induce proper fat mobilization and remodeling of adipose tissue.
Published:
2019-10
Title:
Provocative Question: Should Ketogenic Metabolic Therapy Become the Standard of Care for Glioblastoma?
Authors:
Seyfried, Thomas N.; Shelton, Laura; Arismendi-Morillo, Gabriel; Kalamian, Miriam; Elsakka, Ahmed; Maroon, Joseph; Mukherjee, Purna
Abstract:
No major advances have been made in improving overall survival for glioblastoma (GBM) in almost 100 years. The current standard of care (SOC) for GBM involves immediate surgical resection followed by radiotherapy with concomitant temozolomide chemotherapy. Corticosteroid (dexamethasone) is often prescribed to GBM patients to reduce tumor edema and inflammation. The SOC disrupts the glutamate-glutamine cycle thus increasing availability of glucose and glutamine in the tumor microenvironment. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive GBM growth through substrate level phosphorylation in the cytoplasm and the mitochondria, respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability while elevating ketone bodies that are neuroprotective and non-fermentable. Information is presented from preclinical and case report studies showing how KMT could target tumor cells without causing neurochemical damage thus improving progression free and overall survival for patients with GBM.
Published:
2019-10
Title:
Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: A case report
Authors:
Liu, Hao; Miao, Jing Kun; Yu, Chao Wen; Wan, Ke Xing; Zhang, Juan; Yuan, Zhao Jian; Yang, Jing; Wang, Dong Juan; Zeng, Yan; Zou, Lin
Abstract:
Background: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies. Case presentation: We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C \textgreater T and c.1465delA). Conclusion: This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease.
Published:
2019-10
Title:
The Effectiveness of Intermittent Fasting to Reduce Body Mass Index and Glucose Metabolism: A Systematic Review and Meta-Analysis
Authors:
Cho, Yongin; Hong, Namki; Kim, Kyung-won; joon Cho, Sung; Lee, Minyoung; Lee, Yeon-hee; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Byung-Wan
Abstract:
\textlessp\textgreaterThe effects of an intermittent fasting diet (IFD) in the general population are still controversial. In this study, we aimed to systematically evaluate the effectiveness of an IFD to reduce body mass index and glucose metabolism in the general population without diabetes mellitus. Cochrane, PubMed, and Embase databases were searched to identify randomized controlled trials and controlled clinical trials that compared an IFD with a regular diet or a continuous calorie restriction diet. The effectiveness of an IFD was estimated by the weighted mean difference (WMD) for several variables associated with glucometabolic parameters including body mass index (BMI) and fasting glucose. The pooled mean differences of outcomes were calculated using a random effects model. From 2814 studies identified through a literature search, we finally selected 12 articles (545 participants). Compared with a control diet, an IFD was associated with a significant decline in BMI (WMD, −0.75 kg/m2; 95% CI, −1.44 to −0.06), fasting glucose level (WMD, −4.16 mg/dL; 95% CI, −6.92 to −1.40), and homeostatic model assessment of insulin resistance (WMD, −0.54; 95% CI, −1.05 to −0.03). Fat mass (WMD, −0.98 kg; 95% CI, −2.32 to 0.36) tended to decrease in the IFD group with a significant increase in adiponectin (WMD, 1008.9 ng/mL; 95% CI, 140.5 to 1877.3) and a decrease in leptin (WMD, −0.51 ng/mL; 95% CI, −0.77 to −0.24) levels. An IFD may provide a significant metabolic benefit by improving glycemic control, insulin resistance, and adipokine concentration with a reduction of BMI in adults.\textless/p\textgreater
Published:
2019-10
Title:
Vegan diet in children and adolescents. Recommendations from the French-speaking Pediatric Hepatology, Gastroenterology and Nutrition Group (GFHGNP)
Authors:
Lemale, J.; Mas, E.; Jung, C.; Bellaiche, M.; Tounian, P.; French-speaking Pediatric Hepatology, Gastroenterology and Nutrition Group (GFHGNP)
Abstract:
The current craze for vegan diets has an effect on the pediatric population. This type of diet, which does not provide all the micronutrient requirements, exposes children to nutritional deficiencies. These can have serious consequences, especially when this diet is introduced at an early age, a period of significant growth and neurological development. Even if deficiencies have less impact on older children and adolescents, they are not uncommon and consequently should also be prevented. Regular dietary monitoring is essential, vitamin B12 and vitamin D supplementation is always necessary, while iron, calcium, docosahexaenoic acid, and zinc should be supplemented on a case-by-case basis.
Published:
2019-10
Title:
A pyruvate dehydrogenase complex disorder hypothesis for bipolar disorder
Authors:
Campbell, Iain; Campbell, Harry
Abstract:
Ketosis is a metabolic state in which the body uses ketones derived from breakdown of fatty acids as the primary mitochondrial fuel source instead of glucose. In recent years an accumulation of evidence for the beneficial effects of the ketotic state on the brain have heightened interest in its potential for use in neurological conditions. The ketogenic diet (KD) induces ketosis and is an effective treatment for medically resistant epilepsy. There is significant comorbidity between epilepsy and bipolar disorder (BD) and both conditions are treated by anti-convulsant drugs. In addition, reports on bipolar disease online fora have highlighted subjective mood stabilization effects associated with the KD. These KD reported effects could be explained if there was a disorder in the conversion of pyruvate into Acetyl-CoA (and subsequent impairment of oxidative phosphorylation) which was bypassed by ketones providing an alternative substrate for oxidative phosphorylation. This is consistent with growing evidence that mitochondrial dysfunction plays a causal role in BD and explains the reported TCA cycle dysfunction and elevated pyruvate levels in BD. Reduced levels of ATP affects the normal operation of the Na, K-ATPase in the brain with differing levels of reduction either leading to reduced neuronal action potential and inhibition of neurotransmitter release (consistent with the depressed state in BD) or increased neuronal resting potential and hyper-excitability (consistent with a [hypo]manic mood state). We hypothesize that the mitochondrial dysfunction is due to a disorder of the Pyruvate Dehydrogenase Complex (PDC) and/or Mitochondrial Carrier Protein (MCP) shuttle which moves intracellular pyruvate into mitochondria. The resultant reduction in ATP generation could explain mood instability and cycling in BD (through mechanisms such as those delineated by Mallakh and Peters). This proposed novel causal pathway could explain mood de-stabilization in BD and the reported positive effects of KD. If true, this hypothesis would suggest that there should be increased research attention to PDC (and in particular the E1 alpha subunit) as potential therapeutic targets and further study of a possible role of KD in BD to improve mood stability. Experimental approaches, such as through a clinical trial of KD on mood stabilization in BD, are required to further investigate this hypothesis.
Published:
2019-09
Title:
A short-term religious "fast" from animal products has a minimal impact on cardiometabolic health biomarkers irrespective of concurrent shifts in distinct plant-based food groups
Authors:
Bethancourt, Hilary J; Kratz, Mario; O'Connor, Kathleen
Abstract:
Background Plant-based diets may help improve measures of body fat, blood cholesterol, glucose metabolism, and inflammation. However, limited evidence suggests that the health effects of reducing animal products may depend on the quality of plant-based foods consumed as caloric replacements. Objective This study examined how temporarily restricting consumption of meat, dairy, and egg (MDE) products for religious purposes influences cardiometabolic health biomarkers and whether any effects of MDE restriction on biomarkers are modified by concurrent shifts in calories, fish, and distinct plant-based foods. Design This study followed a sample of 99 individuals in the United States with varying degrees of adherence to Orthodox Christian (OC) guidance to abstain from MDE products during Lent, the 48-d period prior to Easter. Dietary composition was estimated from FFQs and 7-d food records; measures of body fat, blood lipids, glucose metabolism, and inflammation were collected prior to and at the end of Lent. Results Each serving decrease in MDE products was associated with an average −3.7% (95% CI: −5.5%, −2.0%; P
Published:
2019-09
Title:
Chance and predictability in evolution: The genomic basis of convergent dietary specializations in an adaptive radiation
Authors:
Vizueta, Joel; Macías-Hernández, Nuria; Arnedo, Miquel A.; Rozas, Julio; Sánchez-Gracia, Alejandro
Abstract:
The coexistence of multiple eco-phenotypes in independently assembled communities makes island adaptive radiations the ideal framework to test convergence and parallelism in evolution. In the radiation of the spider genus Dysdera in the Canary Islands, species diversification occurs concomitant with repeated events of trophic specialization. These dietary shifts, to feed primarily on woodlice, are accompanied by modifications in morphology (mostly in the mouthparts), behaviour and nutritional physiology. To gain insight into the molecular basis of this adaptive radiation, we performed a comprehensive comparative transcriptome analysis of five Canary Island Dysdera endemics representing two evolutionary and geographically independent events of dietary specialization. After controlling for the potential confounding effects of hemiplasy, our differential gene expression and selective constraint analyses identified a number of genetic changes that could be associated with the repeated adaptations to specialized diet of woodlice, including some related to heavy metal detoxification and homeostasis, the metabolism of some important nutrients and venom toxins. Our results shed light on the genomic basis of an extraordinary case of dietary shift convergence associated with species diversification. We uncovered putative molecular substrates of convergent evolutionary changes at different hierarchical levels, including specific genes, genes with equivalent functions and even particular amino acid positions. This study improves our knowledge of rapid adaptive radiations and provides new insights into the predictability of evolution.
Published:
2019-09
Title:
Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats
Authors:
Guerville, Mathilde; Hamilton, M. Kristina; Ronveaux, Charlotte C.; Ellero-Simatos, Sandrine; Raybould, Helen E.; Boudry, Gaëlle
Abstract:
Purpose: Reduced ability of cholecystokinin (CCK) to induce satiation contributes to hyperphagia and weight gain in high-fat/high-sucrose (HF/HS) diet-induced obesity, and has been linked to altered gut microbiota. Rodent models of obesity use chow or low-fat (LF) diets as control diets; the latter has been shown to alter gut microbiota and metabolome. We aimed to determine whether LF-diet consumption impacts CCK satiation in rats and if so, whether this is prevented by addition of inulin to LF diet. Methods: Rats (n = 40) were fed, for 8 weeks, a chow diet (chow) or low-fat (10%) or high-fat/high-sucrose (45 and 17%, respectively) refined diets with either 10% cellulose (LF and HF/HS) or 10% inulin (LF-I and HF/HS-I). Caecal metabolome was assessed by 1H-NMR-based metabolomics. CCK satiation was evaluated by measuring the suppression of food intake after intraperitoneal CCK injection (1 or 3 µg/kg). Results: LF-diet consumption altered the caecal metabolome, reduced caecal weight, and increased IAP activity, compared to chow. CCK-induced inhibition of food intake was abolished in LF diet-fed rats compared to chow-fed rats, while HF/HS diet-fed rats responded only to the highest CCK dose. Inulin substitution ameliorated caecal atrophy, reduced IAP activity, and modulated caecal metabolome, but did not improve CCK-induced satiety in either LF- or HF/HS-fed rats. Conclusions: CCK signaling is impaired by LF-diet consumption, highlighting that caution must be taken when using LF diet until a more suitable refined control diet is identified.
Published:
2019-09
Title:
Fatty Acid Metabolites Combine with Reduced β Oxidation to Activate Th17 Inflammation in Human Type 2 Diabetes
Authors:
Nicholas, Dequina A.; Proctor, Elizabeth A.; Agrawal, Madhur; Belkina, Anna C.; Van Nostrand, Stephen C.; Panneerseelan-Bharath, Leena; Jones, Albert R.; Raval, Forum; Ip, Blanche C.; Zhu, Min; Cacicedo, Jose M.; Habib, Chloe; Sainz-Rueda, Nestor; Persky, Leah; Sullivan, Patrick G.; Corkey, Barbara E.; Apovian, Caroline M.; Kern, Philip A.; Lauffenburger, Douglas A.; Nikolajczyk, Barbara S.
Abstract:
Published:
2019-09
Title:
Impact of different hypercaloric diets on obesity features in rats: a metagenomics and metabolomics integrative approach
Authors:
Gual-Grau, Andreu; Guirro, Maria; Mayneris-Perxachs, Jordi; Arola, Lluís; Boqué, Noemí
Abstract:
Diet is considered a key influencing agent affecting the gut microbiome. Dysbiosis of microbial communities contributes to the development of metabolic diseases such as obesity. We aimed to characterize the physiological, microbial and metabolic changes induced by different obesogenic diets to understand the diet-specific modulation of the host-microbiota co-metabolism in rodents. For this purpose, Wistar rats were fed standard, cafeteria (CAF), low-fat (LF), high-fat (HF) and high-fat high-sucrose (HFS) diets for 10 weeks. The CAF diet strongly induced an obese phenotype accompanied by dyslipidemia, hyperleptinemia, insulin resistance and hepatic steatosis, whereas both HF and HFS diets promoted overweight. Concerning the microbiome, CAF feeding induced a rise of the Bacteroidetes-to-Firmicutes ratio, while few microbial genera were altered in the HF or HFS group. Changes in microbial activity according to dietary treatment were also reflected in the disruption of short-chain fatty acid production and bile acid metabolism, which were mainly associated with fiber intake. Urinary metabolomics revealed a significant increase in metabolites related to oxidative stress and metabolic inflammation together with an altered excretion of host-microbiota co-metabolites only in the CAF group. Moreover, several associations between metabolic patterns, physiological status and specific microbial communities were described, helping to elucidate the crucial role of the microbiota in host homeostasis. Overall, our study suggests that different hypercaloric dietary models distinctively influence gut microbiota composition and reveals robust and similar clustering patterns concerning both cecal microbiome and urinary metabolome profiles.
Published:
2019-09
Title:
Lipoprotein(a): Current Evidence for a Physiologic Role and the Effects of Nutraceutical Strategies
Authors:
Santos, Heitor O.; Kones, Richard; Rumana, Umme; Earnest, Conrad P.; Izidoro, Luiz F. M.; Macedo, Rodrigo C. O.
Abstract:
PURPOSE: Cardiovascular (CV) diseases account for most worldwide mortality, and a higher level of lipoprotein (Lp)-(a) is recognized as a prevalent contributing risk factor. However, there is no consensus regarding nutritional strategies for lowering Lp(a) concentration. Thus, the purposes of this literature review were to: (1) critically examine data concerning the effects of dietetic interventions and nutraceutical agents on Lp(a) level; and (2) review the feasibility and utility of their clinical use. METHODS: A literature search was conducted for studies published between August 2018 and March 2019. The search was performed using the Cochrane, Medline, and Web of Science databases. In order to expand the research, there were no delimitations on the type or year of the studies. A total of 1932 articles were identified using this search procedure. After duplicates were eliminated, 740 abstracts of articles written in English were screened to identify those of highest relevance. In the final tally, a total of 152 full-text articles were included in this review. FINDINGS: Several foods and decreases in saturated fat and ethanol intake, especially red wine intake, may lower Lp(a) concentration, but limits are necessary. Coffee and tea intake may decrease Lp(a) level; further investigation is crucial before they can be considered potent Lp(a)-lowering agents. Among supplementation strategies, only l-carnitine and coenzyme Q10 are promising clinical candidates to lower Lp(a) level. Since both l-carnitine and coenzyme Q10 supplementation are commonly used for CV support, they deserve further exploration regarding clinical applicability. In contrast, despite potential CV benefits, current research fails to justify use of higher intakes of vitamin C, soy isoflavones, garlic, and ω-3 for decreasing Lp(a) concentration. IMPLICATIONS: Definitive long-term clinical trials are needed to confirm the effects of dietetic interventions and nutraceutical agents on Lp(a) concentration when anticipating improved CV outcomes.
Published:
2019-09
Title:
Comparing the metabolic profiles of raw and cooked pufferfish (Takifugu flavidus) meat by NMR assessment
Authors:
Yang, Luan; Dai, Bona; Ayed, Charfedinne; Liu, Yuan
Abstract:
The difference of metabolite profiles between raw and cooked pufferfish (Takifugu flavidus) meat was explored by 1H NMR technique and multivariate statistical methods. The orthogonal projection to latent structure-discriminant analysis (OPLS-DA) results showed an obvious separation between two samples. There were 24 dominating metabolites in the pufferfish muscle extraction, of which 11 metabolites changed significantly (p<0.05), including 9 amino acids (alanine, leucine, methionine, tyrosine, glutamate, glycine, arginine, lysine, taurine), 1 organic acid (lactate) and 1 alkaloid (betaine). Moreover, the Student's t-test was performed to identify the different levels of metabolites. Sensory intensity experiments showed that there was a significant difference in the umami taste between raw and cooked pufferfish meat (p
Published:
2019-08
Title:
Comparison of protein differences between high- and low-quality goat and bovine parts based on iTRAQ technology
Authors:
Wei, Yanchao; Li, Xin; Zhang, Dequan; Liu, Yongfeng
Abstract:
This study was designed to investigate the differences in the proteomes of high- and low-quality goat and bovine muscles. In total, 364 and 111 differentially expressed proteins (DEPs) were identified in the high-quality/low-quality bovine and goat samples, respectively. The bioinformatic analysis demonstrated that DEPs are involved in glycolysis, the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation. An analysis of quality-related DEPs showed that nicotinamide adenine dinucleotide dehydrogenase (NADH) and succinate dehydrogenase (SDH) could be potential biomarkers for colour, while enolase (ENO) can be used as a marker protein for tenderness qualities in goat. Lactate dehydrogenase (LDH) and 14-3-3 protein can indicate goat and bovine tenderness, while heat-shock proteins (HSPs) can also be used as tenderness marker proteins for different species. Glycerin-3-phosphate dehydrogenase (GPDH) can be used as a protein to detect fat content, and guanine ribonucleotide-binding protein (G protein) may be a flavour marker protein in bovine meat. Copyright © 2019. Published by Elsevier Ltd.
Published:
2019-08
Title:
Effects of urbanization on metabolic syndrome via dietary intake and physical activity in Chinese adults: Multilevel mediation analysis with latent centering
Authors:
Fong, Ted Chun Tat; Ho, Rainbow Tin Hung; Yip, Paul Siu Fai
Abstract:
China has undergone rapid urbanization in the past decades. Metabolic syndrome refers to a cluster of cardiometabolic risk factors such as abdominal obesity, raised blood pressure, and elevated glucose. Existing studies have not explicitly examined the urbanization effect on metabolic syndrome. The present study aims to examine the temporal effects of urbanization on metabolic syndrome in the Chinese context and evaluate dietary intake and physical activity as potential mediating factors. The study sample comprised 6,217 Chinese adults aged between 30 and 65 recruited in 218 communities from 2000 to 2009 waves of the China Health and Nutrition Survey. Growth in urbanization of the communities was derived using latent growth modeling on continuous urbanization index from 2000 to 2009. The participants reported their physical activity and dietary intake. Body mass index and biomarkers were measured at 2009 for diagnosis of metabolic syndrome. Multilevel mediation analysis with novel latent centering approach was conducted across gender to evaluate direct and indirect effects of urbanization on metabolic syndrome via changes in dietary intake and physical activity. The sample displayed linear increasing trends in urbanization, intakes of red meat, dairy products and fast food and declining cereal intake and physical activity with significant inter-individual variations. Controlling for individual-level and community-level covariates, urbanization showed a positive but non-significant direct effect on metabolic syndrome across gender. There were significant and positive indirect effects from urbanization to metabolic syndrome via changes in physical activity in males and via changes in fast food intake in females. The present results highlight the health impact of urbanization as a dynamic process at the community level on metabolic syndrome via different indirect pathways of lifestyle factors across gender. Methodological and practical implications are discussed in relation to these modifiable lifestyle factors in the urbanizing Chinese society. • 6,217 Chinese adults from the 2000-2009 waves of China Health and Nutrition Survey. • The urbanization effect analysed using multilevel mediation with latent centering. • The study sample showed increasing dietary intakes and declining physical activity. • Urbanization positively predicted metabolic syndrome via physical activity in male. • Urbanization positively predicted metabolic syndrome via fastfood intake in female.
Published:
2019-08
Title:
Individual characteristics associated with changes in the contribution of plant foods to dietary intake in a French prospective cohort
Authors:
Colombet, Zoé; Allès, Benjamin; Si Hassen, Wendy; Lampuré, Aurélie; Kesse-Guyot, Emmanuelle; Péneau, Sandrine; Hercberg, Serge; Méjean, Caroline
Abstract:
PURPOSE: Rebalancing the contribution of animal- and plant-based foods is needed to achieve sustainable diet. However, little is known concerning individual characteristics that may influence intake of plant-based foods and their changes over time. We aimed to assess changes in the contribution of plant-based foods to dietary intake over time and their association with individual characteristics. METHODS: The contribution of plant-based foods was assessed by percent energy intake provided by plant proteins in diet (PEIPP) and a score of adherence to a pro-vegetarian diet, using repeated 24-h records in 15,615 French adults participating in the NutriNet-Santé cohort study. Associations between baseline individual characteristics and changes in the two indicators over a 4-6-year follow-up were assessed using a linear mixed model. RESULTS: At baseline, PEIPP and pro-vegetarian score were positively associated with age [β65+ = 0.80, 95% CI = (0.71, 0.88), β65+ = 3.30, 95% CI = (2.97, 3.64), respectively] and education [βpostgraduate = 0.23, 95% CI = (0.12, 0.34), βpostgraduate = 1.19, 95% CI = (0.75, 1.62)], while they were inversely associated with BMI class [βobesity = - 0.48, 95% CI = (0.56, 0.41), βobesity = - 2.31, 95% CI = (- 2.63, - 1.98)]. Men had higher PEIPP than women [β = 0.06, 95% CI = (0.01, 0.11)]. Pro-vegetarian score significantly increased over time [β = 0.23, 95% CI = (0.08, 0.37)]. The older the individual at baseline, the greater the decrease in the two indicators during follow-up. Pro-vegetarian score increased during follow-up for obese participants at baseline. CONCLUSIONS: The contribution of plant-based foods was associated with several socio-demographic and economic characteristics at baseline, whereas change over time was related to age and weight status. Further analysis of individual obstacles and lever to consume plant-based foods is needed.
Published:
2019-08
Title:
Locally renewing resident synovial macrophages provide a protective barrier for the joint
Authors:
Culemann, Stephan; Grüneboom, Anika; Nicolás-Ávila, José Ángel; Weidner, Daniela; Lämmle, Katrin Franziska; Rothe, Tobias; Quintana, Juan A.; Kirchner, Philipp; Krljanac, Branislav; Eberhardt, Martin; Ferrazzi, Fulvia; Kretzschmar, Elke; Schicht, Martin; Fischer, Kim; Gelse, Kolja; Faas, Maria; Pfeifle, René; Ackermann, Jochen A.; Pachowsky, Milena; Renner, Nina; Simon, David; Haseloff, Reiner F.; Ekici, Arif B.; Bäuerle, Tobias; Blasig, Ingolf E.; Vera, Julio; Voehringer, David; Kleyer, Arnd; Paulsen, Friedrich; Schett, Georg; Hidalgo, Andrés; Krönke, Gerhard
Abstract:
Published:
2019-08
Title:
Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI
Authors:
Matsuzawa, Yasushi; Nakahashi, Hidefumi; Konishi, Masaaki; Sato, Ryosuke; Kawashima, Chika; Kikuchi, Shinnosuke; Akiyama, Eiichi; Iwahashi, Noriaki; Maejima, Nobuhiko; Okada, Kozo; Ebina, Toshiaki; Hibi, Kiyoshi; Kosuge, Masami; Ishigami, Tomoaki; Tamura, Kouichi; Kimura, Kazuo
Abstract:
Trimethylamine N-oxide (TMAO), a metabolite derived from the gut microbiota, is proatherogenic and associated with cardiovascular events. However, the change in TMAO with secondary prevention therapies for ST-segment elevation acute myocardial infarction (STEMI) remains unclear. The purpose of this study was to investigate the sequential change in TMAO levels in response to the current secondary prevention therapies in patients with STEMI and the clinical impact of TMAO levels on cardiovascular events We included 112 STEMI patients and measured plasma TMAO levels at the onset of STEMI and 10 months later (chronic phase). After the chronic-phase assessment, patients were followed up for cardiovascular events. Plasma TMAO levels significantly increased from the acute phase to the chronic phase of STEMI (median: 5.63 to 6.76 μM, P = 0.048). During a median period of 5.4 years, 17 patients experienced events. The chronic-phase TMAO level independently predicted future cardiovascular events (adjusted hazard ratio for 0.1 increase in log chronic-phase TMAO level: 1.343, 95% confidence interval 1.122–1.636, P = 0.001), but the acute-phase TMAO level did not. This study demonstrated the clinical importance of the chronic-phase TMAO levels on future cardiovascular events in patients after STEMI.
Published:
2019-08
Title:
Nutritional modulation of the epigenome and its implication for future health
Authors:
Burton, Mark A.; Lillycrop, Karen A.
Abstract:
Non-communicable diseases (NCD) such as type-2 diabetes and CVD are now highly prevalent in both developed and developing countries. Evidence from both human and animal studies shows that early-life nutrition is an important determinant of NCD risk in later life. The mechanism by which the early-life environment influences future disease risk has been suggested to include the altered epigenetic regulation of gene expression. Epigenetic processes regulate the accessibility of genes to the cellular proteins that control gene transcription, determining where and when a gene is switched on and its level of activity. Epigenetic processes not only play a central role in regulating gene expression but also allow an organism to adapt to the environment. In this review, we will focus on how both maternal and paternal nutrition can alter the epigenome and the evidence that these changes are causally involved in determining future disease risk.
Published:
2019-08
Title:
Synchronous rise of African C 4 ecosystems 10 million years ago in the absence of aridification
Authors:
Polissar, Pratigya J.; Rose, Cassaundra; Uno, Kevin T.; Phelps, Samuel R.; deMenocal, Peter
Abstract:
Aridification did not cause the expansion of ecosystems using the C4 photosynthetic pathway in parts of Africa 10 million years ago, according to leaf-wax analyses in deep-sea drill cores, leaving declining atmospheric carbon dioxide levels as the most plausible cause.
Published:
2019-08
Title:
The Cytokine TNF Promotes Transcription Factor SREBP Activity and Binding to Inflammatory Genes to Activate Macrophages and Limit Tissue Repair
Authors:
Kusnadi, Anthony; Park, Sung Ho; Yuan, Ruoxi; Pannellini, Tania; Giannopoulou, Eugenia; Oliver, David; Lu, Theresa; Park-Min, Kyung-Hyun; Ivashkiv, Lionel B.
Abstract:
Published:
2019-08
Title:
Usefulness of Monocytes/macrophages Activated With Low-dose Lipopolysaccharide in Tumor Tissue and Adipose Tissue of Obesity
Authors:
Honda, Teruko; Inagawa, Hiroyuki
Abstract:
Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/ macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 β, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.
Published:
2019-08
Title:
A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate
Authors:
Wang, Wenshan; Ishibashi, Jeff; Trefely, Sophie; Shao, Mengle; Cowan, Alexis J.; Sakers, Alexander; Lim, Hee-Woong; O’Connor, Sean; Doan, Mary T.; Cohen, Paul; Baur, Joseph A.; King, M. Todd; Veech, Richard L.; Won, Kyoung-Jae; Rabinowitz, Joshua D.; Snyder, Nathaniel W.; Gupta, Rana K.; Seale, Patrick
Abstract:
Published:
2019-07
Title:
ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression
Authors:
Tameire, Feven; Verginadis, Ioannis I.; Leli, Nektaria Maria; Polte, Christine; Conn, Crystal S.; Ojha, Rani; Salinas, Carlo Salas; Chinga, Frank; Monroy, Alexandra M.; Fu, Weixuan; Wang, Paul; Kossenkov, Andrew; Ye, Jiangbin; Amaravadi, Ravi K.; Ignatova, Zoya; Fuchs, Serge Y.; Diehl, J. Alan; Ruggero, Davide; Koumenis, Constantinos
Abstract:
Activating transcription factor 4 (ATF4) promotes MYC-driven tumour progression. Tameire et al. identify ATF4 and its target eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) as regulators of MYC-mediated amino acid biosynthesis and protein synthesis, thereby modulating tumour progression and survival in mice.
Published:
2019-07
Title:
Acute fructose intake suppresses fasting-induced hepatic gluconeogenesis through the AKT-FoxO1 pathway
Authors:
Sato, Tomoki; Watanabe, Yui; Nishimura, Yuri; Inoue, Mizuki; Morita, Akihito; Miura, Shinji
Abstract:
Excessive intake of fructose increases lipogenesis in the liver, leading to hepatic lipid accumulation and development of fatty liver disease. Metabolic alterations in the liver due to fructose intake have been reported in many studies, but the effect of fructose administration on hepatic gluconeogenesis is not fully understood. The aim of this study was to evaluate the acute effects of fructose administration on fasting-induced hepatic gluconeogenesis. C57BL/6J mice were administered fructose solution after 14 h of fasting and plasma insulin, glucose, free fatty acids, and ketone bodies were analysed. We also measured phosphorylated AKT and forkhead box O (FoxO) 1 protein levels and gene expression related to gluconeogenesis in the liver. Furthermore, we measured glucose production from pyruvate after fructose administration. Glucose-administered mice were used as controls. Fructose administration enhanced phosphorylation of AKT in the liver, without increase of blood insulin levels. Blood free fatty acids and ketone bodies concentrations were as high as those in the fasting group after fructose administration, suggesting that insulin-induced inhibition of lipolysis did not occur in mice administered with fructose. Fructose also enhanced phosphorylation of FoxO1 and suppressed gluconeogenic gene expression, glucose-6-phosphatase activity, and glucose production from pyruvate. The present study suggests that acute fructose administration suppresses fasting-induced hepatic gluconeogenesis in an insulin-independent manner.
Published:
2019-07
Title:
Comparative isotopic evidence from East Turkana supports a dietary shift within the genus Homo
Authors:
Patterson, David B.; Braun, David R.; Allen, Kayla; Barr, W. Andrew; Behrensmeyer, Anna K.; Biernat, Maryse; Lehmann, Sophie B.; Maddox, Tom; Manthi, Fredrick K.; Merritt, Stephen R.; Morris, Sarah E.; O’Brien, Kaedan; Reeves, Jonathan S.; Wood, Bernard A.; Bobe, René
Abstract:
Carbon and oxygen isotope analysis of sediments and soils from hominin locales in Kenya coupled with results from hominin taxa suggest that a dietary shift from C3 to C4 resources occurred in the genus Homo circa 1.65 million years ago despite palaeoenvironmental continuity.
Published:
2019-07
Title:
Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E
Authors:
Fritscher-Ravens, Annette; Pflaum, Theresa; Mösinger, Marie; Ruchay, Zino; Röcken, Christoph; Milla, Peter J.; Das, Melda; Böttner, Martina; Wedel, Thilo; Schuppan, Detlef
Abstract:
Published:
2019-07
Title:
Role and therapeutic potential of dietary ketone bodies in lymph vessel growth
Authors:
García-Caballero, Melissa; Zecchin, Annalisa; Souffreau, Joris; Truong, Anh-Co Khanh; Teuwen, Laure-Anne; Vermaelen, Wesley; Martín-Pérez, Rosa; de Zeeuw, Pauline; Bouché, Ann; Vinckier, Stefan; Cornelissen, Ivo; Eelen, Guy; Ghesquière, Bart; Mazzone, Massimiliano; Dewerchin, Mieke; Carmeliet, Peter
Abstract:
Published:
2019-07
Title:
Serum metabolite profiles of habitual diet: evaluation by 1 H-nuclear magnetic resonance analysis
Authors:
Lindqvist, Helen M; Rådjursöga, Millie; Malmodin, Daniel; Winkvist, Anna; Ellegård, Lars
Abstract:
Background Objective and reliable methods to measure dietary exposure and prove associations and causation between diet and health are desirable. Objective The aim of this study was to investigate if 1H-nuclear magnetic resonance (1H-NMR) analysis of serum samples may be used as an objective method to discriminate vegan, vegetarian, and omnivore diets. Specifically, the aim was to identify a metabolite pattern that separated meat-eaters from non–meat-eaters and vegans from nonvegans. Methods Healthy volunteers (45 men and 75 women) complying with habitual vegan (n = 43), vegetarian (n = 24 + vegetarians adding fish n = 13), or omnivore (n = 40) diets were enrolled in the study. Data were collected on clinical phenotype, body composition, lifestyle including a food-frequency questionnaire (FFQ), and a 4-d weighed food diary. Serum samples were analyzed by routine clinical test and for metabolites by 1H-NMR spectroscopy. NMR data were nonnormalized, UV-scaled, and analyzed with multivariate data analysis [principal component analysis, orthogonal projections to latent structures (OPLS) and OPLS with discriminant analysis]. In the multivariate analysis volunteers were assigned as meat-eaters (omnivores), non–meat-eaters (vegans and vegetarians), vegans, or nonvegans (lacto-ovo-vegetarians, vegetarians adding fish, and omnivores). Metabolites were identified by line-fitting of 1D 1H-NMR spectra and the use of statistical total correlation spectroscopy. Results Although many metabolites differ in concentration between men and women as well as by age, body mass index, and body composition, it was possible to correctly classify 97.5% of the meat-eaters compared with non–meat-eaters and 92.5% of the vegans compared with nonvegans. The branched-chain amino acids, creatine, lysine, 2-aminobutyrate, glutamine, glycine, trimethylamine, and 1 unidentified metabolite were among the most important metabolites in the discriminating patterns in relation to intake of both meat and other animal products. Conclusions 1H-NMR serum metabolomics appears to be a possible objective tool to identify and predict habitual intake of meat and other animal products in healthy subjects. These results should be confirmed in larger cohort studies or intervention trials. This trial was registered at clinicaltrials.gov as NCT02039609.
Published:
2019-07
Title:
Suppression of Brown Adipocyte Autophagy Improves Energy Metabolism by Regulating Mitochondrial Turnover
Authors:
Kim, Donghwan; Kim, Ji-Hye; Kang, Young-Ho; Kim, Je Seong; Yun, Sung-Cheol; Kang, Sang-Wook; Song, Youngsup
Abstract:
The high abundance of mitochondria and the expression of mitochondrial uncoupling protein 1 (UCP1) confer upon brown adipose tissue (BAT) the unique capacity to convert chemical energy into heat at the expense of ATP synthesis. It was long believed that BAT is present only in infants, and so, it was not considered as a potential therapeutic target for metabolic syndrome; however, the discovery of metabolically active BAT in adult humans has re-stimulated interest in the contributions of BAT metabolic regulation and dysfunction to health and disease. Here we demonstrate that brown adipocyte autophagy plays a critical role in the regulation BAT activity and systemic energy metabolism. Mice deficient in brown adipocyte autophagy due to BAT-specific deletion of Atg7—a gene essential for autophagosome generation—maintained higher mitochondrial content due to suppression of mitochondrial clearance and exhibited improved insulin sensitivity and energy metabolism. Autophagy was upregulated in BAT of older mice compared to younger mice, suggesting its involvement in the age-dependent decline of BAT activity and metabolic rate. These findings suggest that brown adipocyte autophagy plays a crucial role in metabolism and that targeting this pathway may be a potential therapeutic strategy for metabolic syndrome.
Published:
2019-07
Title:
The Preventive Effects of Greenshell Mussel (Perna canaliculus) on Early-Stage Metabolic Osteoarthritis in Rats with Diet-Induced Obesity
Authors:
Siriarchavatana, Parkpoom; Kruger, Marlena C.; Miller, Matthew R.; Tian, Hong Sabrina; Wolber, Frances M.
Abstract:
The prevalence of osteoarthritis (OA) is rising worldwide, with the most pronounced increase being in the category of metabolic-associated osteoarthritis (MetOA). This is predicted to worsen with the global rise in aging societies and obesity. To address this health burden, research is being conducted to identify foods that can reduce the incidence or severity of MetOA. Oil from the Greenshell mussel (Perna canaliculus) (GSM), a native New Zealand shellfish, has been successfully used to reduce OA symptoms. The current study assessed the effect of including flash-dried powder from whole GSM meat as part of a normal (control) versus high-fat/high-sugar (HFHS) diet for 13 weeks on the development of MetOA in rats. Rats fed a HFHS diet developed metabolic dysregulation and obesity with elevated plasma leptin and HbA1C concentrations. Visible damage to knee joint cartilage was minimal, but plasma levels of C telopeptide of type II collagen (CTX-II), a biomarker of cartilage degradation, were markedly higher in HFHS-fed rats compared to control-fed rats. However, rats fed the HFHS diet containing GSM had significantly reduced serum CTX-II. Inclusion of GSM in rats fed the control diet also lowered CTX-II. These findings suggest that dietary GSM can reduce the incidence or slow the progression of early MetOA.
Published:
2019-07
Title:
Very Low Crude Protein and Varying Glycine Concentrations in the Diet Affect Growth Performance, Characteristics of Nitrogen Excretion, and the Blood Metabolome of Broiler Chickens
Authors:
Hofmann, Philipp; Siegert, Wolfgang; Kenéz, Ákos; Naranjo, Victor D; Rodehutscord, Markus
Abstract:
Background: The minimum to which dietary crude protein (CP) level for broiler chickens can be reduced without decreasing growth and the glycine equivalent (Glyequi) concentration required are not known. The plasma metabolome might reflect dietary influences on physiological processes.Objective: The aim of this study was to investigate the effect of 3 low CP levels with 4 Glyequi concentrations on growth and characteristics of nitrogen excretion, and to identify plasma metabolome variations.Methods: Male Ross308 broiler chickens were provided 1 of 12 dietary treatments in 84 metabolism cages (10/cage) from days 7 to 21. Three diets with 163 (CP163), 147 (CP147), and 132 (CP132) g CP/kg were formulated, each containing 12, 15, 18, and 21 g Glyequi/kg. Essential amino acid concentrations were the same in all diets. Animals and feed were weighed on days 7 and 21 to determine average daily gain (ADG) and gain:feed ratio (G:F). Excreta were collected from days 18 to 21 to analyze nitrogenous components, and blood was obtained on day 21 to conduct a metabolome analysis.Results: Two-factor ANOVA showed significant interaction effects for ADG, G:F, and nitrogen efficiency (P
Published:
2019-07
Title:
Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment
Authors:
Bu, Luke; Baba, Hideo; Yoshida, Naoya; Miyake, Keisuke; Yasuda, Tadahito; Uchihara, Tomoyuki; Tan, Patrick; Ishimoto, Takatsugu
Abstract:
Increasing lines of evidence show that the malignant behavior of cancer is not exclusively attributable to cancer cells but also radically influenced by cancerous stroma activity and controlled through various mechanisms by the microenvironment. In addition to structural components, such as the extracellular matrix, stromal cells, such as macrophages, endothelial cells, and specifically cancer-associated fibroblasts (CAFs), have attracted substantial attention over recent decades. CAFs provide routes for aggressive carcinomas and contribute to invasion and metastasis through the biochemical alteration and regulation of cancer-related pathways. However, another facet of CAFs that has been neglected by numerous studies is that CAFs might serve as a negative regulator of cancer progression under certain circumstances. The various origins of CAFs, the diverse tissues in which they reside and their interactions with different cancer cells appear to be responsible for this inconsistency. This review summarizes the latest knowledge regarding CAF heterogeneity and offers a novel perspective and a beneficial approach for obtaining an improved understanding of CAFs.
Published:
2019-06
Title:
Corrigendum to "Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base" [Nutrition 31 (2015) 1-13]
Authors:
Feinman, Richard D.; Pogozelski, Wendy K.; Astrup, Arne; Bernstein, Richard K.; Fine, Eugene J.; Westman, Eric C.; Accurso, Anthony; Frassetto, Lynda; Gower, Barbara A.; McFarlane, Samy I.; Nielsen, Jörgen Vesti; Krarup, Thure; Saslow, Laura; Roth, Karl S.; Vernon, Mary C.; Volek, Jeff S.; Wilshire, Gilbert B.; Dahlqvist, Annika; Sundberg, Ralf; Childers, Ann; Morrison, Katharine; Manninen, Anssi H.; Dashti, Hussain M.; Wood, Richard J.; Wortman, Jay; Worm, Nicolai
Abstract:
Published:
2019-06
Title:
Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort: An Epi-IBD study
Authors:
Burisch, Johan; Zammit, Stefania Chetcuti; Ellul, Pierre; Turcan, Svetlana; Duricova, Dana; Bortlik, Martin; Andersen, Karina Winther; Andersen, Vibeke; Kaimakliotis, Ioannis P.; Fumery, Mathurin; Gower-Rousseau, Corinne; Girardin, Giulia; Valpiani, Daniela; Goldis, Adrian; Brinar, Marko; Čuković-Čavka, Silvija; Oksanen, Pia; Collin, Pekka; Barros, Luisa; Magro, Fernando; Misra, Ravi; Arebi, Naila; Eriksson, Carl; Halfvarson, Jonas; Kievit, Hendrika Adriana Linda; Pedersen, Natalia; Kjeldsen, Jens; Myers, Sally; Sebastian, Shaji; Katsanos, Konstantinos H.; Christodoulou, Dimitrios K.; Midjord, Jóngerð; Nielsen, Kári Rubek; Kiudelis, Gediminas; Kupcinskas, Limas; Nikulina, Inna; Belousova, Elena; Schwartz, Doron; Odes, Selwyn; Salupere, Riina; Carmona, Amalia; Pineda, Juan R.; Vegh, Zsuzsanna; Lakatos, Peter L.; Langholz, Ebbe; Munkholm, Pia; Epi-IBD group
Abstract:
BACKGROUND AND AIM: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years. METHODS: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period. RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
Published:
2019-06
Title:
Hair Metabolomics in Animal Studies and Clinical Settings
Authors:
Jang, Won-Jun; Choi, Jae Yoon; Park, Byoungduck; Seo, Ji Hae; Seo, Young Ho; Lee, Sangkil; Jeong, Chul-Ho; Lee, Sooyeun
Abstract:
Metabolomics is a powerful tool used to understand comprehensive changes in the metabolic response and to study the phenotype of an organism by instrumental analysis. It most commonly involves mass spectrometry followed by data mining and metabolite assignment. ...
Published:
2019-06
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