Effects of Casein, Chicken, and Pork Proteins on the Regulation of Body Fat and Blood Inflammatory Factors and Metabolite Patterns Are Largely Dependent on the Protein Level and Less Attributable to the Protein Source
Song, Shangxin ; Xia, Tianlan ; Zhu, Changqing ; Xue, Jingqi ; Fu, Qingquan ; Hua, Chun ; Hooiveld, Guido J.E.J. ; Müller, Michael ; Li, Chunbao - \ 2020
Journal of Agricultural and Food Chemistry 68 (2020)35. - ISSN 0021-8561 - p. 9398 - 9407.
high-fat diet - meat protein - obesity - rats - untargeted metabolomics
The impact of meat protein on metabolic regulation is still disputed and may be influenced by protein level. This study aimed to explore the effects of casein, pork, and chicken proteins at different protein levels (40% E vs 20% E) on body weight regulation, body fat accumulation, serum hormone levels, and inflammatory factors/metabolites in rats maintained on high-fat (45% E fat) diets for 84 d. Increased protein levels resulted in a significant reduction in body fat mass and an increase in the serum levels of the anti-inflammatory cytokine IL-10, independent of protein source. Analysis of blood via untargeted metabolomics analysis identified eight, four, and four metabolites significantly altered by protein level, protein source, and a protein level-source interaction, respectively. Together, the effects of casein, chicken, and pork protein on the regulation of body fat accumulation and blood metabolite profile are largely dependent on protein level and less attributable to the protein source.
A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice
Kuipers, Eline N. ; Held, Ntsiki M. ; Het Panhuis, Wietse In; Modder, Melanie ; Ruppert, Philip M.M. ; Kersten, Sander ; Kooijman, Sander ; Guigas, Bruno ; Houtkooper, Riekelt H. ; Rensen, Patrick C.N. ; Boon, Mariëtte R. - \ 2019
American Journal of Physiology. Endocrinology and Metabolism 317 (2019)5. - ISSN 0193-1849 - p. E820 - E830.
brown adipose tissue - high-fat diet - lipid accumulation - macrophage - mitochondrial dynamics
Brown adipose tissue (BAT) catabolizes glucose and fatty acids to produce heat and thereby contributes to energy expenditure. Long-term high-fat diet (HFD) feeding results in so-called 'whitening' of BAT characterized by increased lipid deposition, mitochondrial dysfunction, and reduced fat oxidation. The aim of the current study was to unravel the rate and related mechanisms by which HFD induces BAT whitening and insulin resistance. Wild-type mice were fed a HFD for 0, 1, 3, or 7 days. Within 1 day of HFD, BAT weight and lipid content were increased. HFD also immediately reduced insulin-stimulated glucose uptake by BAT, indicating rapid induction of insulin resistance. This was accompanied by a tendency toward a reduced uptake of triglyceride-derived fatty acids by BAT. Mitochondrial mass and Ucp1 expression were unaltered, whereas after 3 days of HFD, markers of mitochondrial dynamics suggested induction of a more fused mitochondrial network. Additionally, HFD also increased macrophage markers in BAT after 3 days of HFD. Counterintuitively, the switch to HFD was accompanied by an acute rise in core body temperature. We showed that a single day of HFD feeding is sufficient to induce the first signs of whitening and insulin resistance in BAT, which reduces the uptake of glucose and triglyceride-derived fatty acids. BAT whitening and insulin resistance are likely sustained by reduced mitochondrial oxidation due to changes in mitochondrial dynamics and macrophage infiltration, respectively. Likely, the switch to HFD swiftly induces thermogenesis in other metabolic organs, which allows attenuation of BAT thermogenesis.
Lipoprotein lipase in mouse kidney : effects of nutritional status and high-fat diet
Nyrén, Rakel ; Makoveichuk, Elena ; Malla, Sandhya ; Kersten, Sander ; Nilsson, Stefan K. ; Ericsson, Madelene ; Olivecrona, Gunilla - \ 2019
American Journal of Physiology : Renal Physiology 316 (2019)3. - ISSN 1931-857X - p. F558 - F571.
angiopoietin-like protein 4 - high-fat diet - lipoprotein lipase - mouse - triglyceride uptake
Activity of lipoprotein lipase (LPL) is high in mouse kidney, but the reason is poorly understood. The aim was to characterize localization, regulation, and function of LPL in kidney of C57BL/6J mice. We found LPL mainly in proximal tubules, localized inside the tubular epithelial cells, under all conditions studied. In fed mice, some LPL colocalized with the endothelial markers CD31 and GPIHBP1 and could be removed by perfusion with heparin, indicating a vascular location. The role of angiopoietin-like protein 4 (ANGPTL4) for nutritional modulation of LPL activity was studied in wild-type and Angptl4-/- mice. In Angptl4-/- mice, kidney LPL activity remained high in fasted animals, indicating that ANGPTL4 is involved in suppression of LPL activity on fasting, like in adipose tissue. The amount of ANGPTL4 protein in kidney was low, and the protein appeared smaller in size, compared with ANGPTL4 in heart and adipose tissue. To study the influence of obesity, mice were challenged with high-fat diet for 22 wk, and LPL was studied after an overnight fast compared with fasted mice given food for 3 h. High-fat diet caused blunting of the normal adaptation of LPL activity to feeding/fasting in adipose tissue, but in kidneys this adaptation was lost only in male mice. LPL activity increases to high levels in mouse kidney after feeding, but as no difference in uptake of chylomicron triglycerides in kidneys is found between fasted and fed states, our data confirm that LPL appears to have a minor role for lipid uptake in this organ.
Molecular mechanisms underlying the potential antiobesity-related diseases effect of cocoa polyphenols
Ali, F. ; Ismail, A. ; Kersten, A.H. - \ 2014
Molecular Nutrition & Food Research 58 (2014)1. - ISSN 1613-4125 - p. 33 - 48.
low-density-lipoprotein - diet-induced obesity - flavanol-rich cocoa - high-fat diet - nf-kappa-b - ldl oxidative susceptibility - alpha-mediated inflammation - insulin-resistance - dark chocolate - in-vitro
Obesity and related metabolic diseases (e.g., type 2 diabetes, cardiovascular diseases, and hypertension) are the most prevailing nutrition-related issues in the world. An emerging feature of obesity is their relationship with chronic inflammation that begins in white adipose tissue and eventually becomes systemic. One potential dietary strategy to reduce glucose intolerance and inflammation is consumption of polyphenol-rich cocoa-like cocoa or their by-products. In vitro as well as in vivo data indicate that cocoa polyphenols (CPs) may exhibit antioxidant and anti-inflammatory properties. Polyphenols commonly found in cocoa have been reported to regulate lipid metabolism via inducing metabolic gene expression or activating transcription factors that regulate the expression of numerous genes, many of which play an important role in energy metabolism. Currently, several molecular targets (e.g., nuclear factor Kappa B, activated protein-1, peroxisome proliferator-activated receptors, liver X receptors, and adiponectin gene) have been identified, which may explain potential beneficial obesity-associated diseases effects of CPs. Further studies have been performed regarding the protective effects of CPs against metabolic diseases by suppressing transcription factors that antagonize lipid accumulation. Thus, polyphenols-rich cocoa products may diminish obesity-mediated metabolic diseases by multiple mechanisms, thereby attenuating chronic inflammation.
Intestinal permeability - a new target for disease prevention and therapy
Bischoff, S.C. ; Barbara, G. ; Buurman, W. ; Ockhuizen, T. ; Schulzke, J.D. ; Serino, M. ; Tilg, H. ; Watson, A. ; Wells, J.M. - \ 2014
BMC Gastroenterology 14 (2014). - ISSN 1471-230X - 25 p.
irritable-bowel-syndrome - placebo-controlled trial - enteropathogenic escherichia-coli - severe acute-pancreatitis - helicobacter-pylori caga - high-fat diet - clostridium-difficile infection - serotonin reuptake transporter - epithelial barrier function - apical
Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms ‘intestinal barrier’ and ‘intestinal permeability’ are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by ‘intestinal permeability’. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and – more recently recognized – obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.
IL-37 protects against obesity-induced inflammation and insulin resistance
Ballak, D.B. ; Diepen, J.A. van; Moschen, A.R. ; Jansen, H. ; Hijmans, A. ; Groenhof, G.J. ; Leenders, F. ; Bufler, P. ; Boekschoten, M.V. - \ 2014
Nature Communications 5 (2014). - ISSN 2041-1723 - 12 p.
white adipose-tissue - high-fat diet - human interleukin-1-alpha - innate immunity - beta-cells - mice - receptor - family - expression - members
Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member ¿IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human ¿IL-37 (¿IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of ¿adiponectin and preserved ¿glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant ¿IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state ¿IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal ¿IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that ¿IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.
Nutrigenomics of Body Weight Regulation: A Rationale for Careful Dissection of Individual Contributors
Keijer, J. ; Hoevenaars, F.P.M. ; Nieuwenhuizen, A.G. ; Schothorst, E.M. van - \ 2014
Nutrients 6 (2014)10. - ISSN 2072-6643 - p. 4531 - 4551.
blood mononuclear-cells - diet-induced obesity - high-fat diet - adipose-tissue - metabolic-rate - adaptive thermogenesis - food-intake - nutrition transition - energy-requirements - mass-spectrometry
Body weight stability may imply active regulation towards a certain physiological condition, a body weight setpoint. This interpretation is ill at odds with the world-wide increase in overweight and obesity. Until now, a body weight setpoint has remained elusive and the setpoint theory did not provide practical clues for body weight reduction interventions. For this an alternative theoretical model is necessary, which is available as the settling point model. The settling point model postulates that there is little active regulation towards a predefined body weight, but that body weight settles based on the resultant of a number of contributors, represented by the individual’s genetic predisposition, in interaction with environmental and socioeconomic factors, such as diet and lifestyle. This review refines the settling point model and argues that by taking body weight regulation from a settling point perspective, the road will be opened to careful dissection of the various contributors to establishment of body weight and its regulation. This is both necessary and useful. Nutrigenomic technologies may help to delineate contributors to body weight settling. Understanding how and to which extent the different contributors influence body weight will allow the design of weight loss and weight maintenance interventions, which hopefully are more successful than those that are currently available.
PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism
Diepen, J.A. van; Jansen, P.A. ; Ballak, D.B. ; Hijmans, A. ; Hooiveld, G.J.E.J. ; Rommelaere, S. ; Kersten, A.H. ; Stienstra, R. - \ 2014
Journal of Hepatology 61 (2014)2. - ISSN 0168-8278 - p. 366 - 372.
high-fat diet - gene-expression - insulin-resistance - null mice - liver - cysteamine - tissue - acids - hepatocytes - fenofibrate
Background & Aims Peroxisome proliferator-activated receptor alpha (PPARa) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARa target gene in liver, but its function in hepatic lipid metabolism is unknown. Methods We investigated the regulation of vanin-1, and total vanin activity, by PPARa in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Results Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPARa activity. In addition, activation of mouse PPARa regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPARa, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPARa agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. Conclusions We show that hepatic vanin-1 is under extremely sensitive regulation by PPARa and that plasma vanin activity could serve as a readout of changes in PPARa activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting. Abbreviations PPAR, Peroxisome proliferator-activated receptor; RXR, Retinoid X Receptor; VNN1, vanin-1; VNN2, vanin-2; VNN3, vanin-3; WT, wild-type; BMI, body mass index; Pan-AMC, pantothenate-7-amino-4-methylcoumarin; TG, Triglycerides; TC, total cholesterol; FFA, free fatty acids; KLF15, Kruppel-like factor 15; STAT3, signal transducer and activator of transcription 3; SP1, trans-acting transcription factor 1; CBFB, core binding factor beta; XBP1, x-box binding protein 1; NAFLD, non-alcoholic fatty liver disease; Pan-PNa, pantothenate-4-nitroanilide; Abcd2, chemokine (C-C motif) ligand 17; Acadm, acyl-CoA dehydrogenase, medium chain; Acot1, acyl-CoA thioesterase 1; Acot2, acyl-CoA thioesterase 2; Acsl5, acyl-CoA synthetase long-chain family member 5; Ehhadh, enoyl-CoA hydratase/3-hydroxylacyl CoA dehydrogenase; NASH, non-alcoholic steatohepatitis (NASH)
Impact of Diet on Human Intestinal Microbiota and Health
Salonen, A. ; Vos, W.M. de - \ 2014
Annual Review of Food Science and Technology 5 (2014). - ISSN 1941-1413 - p. 239 - 262.
human gut microbiota - high-fat diet - total parenteral-nutrition - irritable-bowel-syndrome - colon-cancer risk - induced obesity - bile-acids - lipid-metabolism - crohns-disease - akkermansia-muciniphila
Our intestinal microbiota is involved in the breakdown and bioconversion of dietary and host components that are not degraded and taken up by our own digestive system. The end products generated by our microbiota fuel our enterocytes and support growth but also have signaling functions that generate systemic immune and metabolic responses. Due to the immense metabolic capacity of the intestinal microbiota and its relatively high plasticity, there is great interest in identifying dietary approaches that allow intentional and predictable modulation of the microbiota. In this article, we review the current insights on dietary influence on the human intestinal microbiota based on recent high-throughput molecular studies and interconnections with health. We focus especially on the emerging data that identify the amount and type of dietary fat as significant modulators of the colonic microbiota and its metabolic output.
Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome
Sailer, M. ; Dahlhoff, C. ; Giesbertz, P. ; Eidens, M.K. ; Wit, N.J.W. de; Rubio-Aliaga, I. ; Boekschoten, M.V. ; Müller, M.R. ; Daniel, H. - \ 2013
PLoS ONE 8 (2013)5. - ISSN 1932-6203
amino-acid transporter - skeletal-muscle cells - arginine bioavailability ratios - high-fat diet - insulin-resistance - l-alanine - protein - liver - secretion - mechanism
Article About the Authors Metrics Comments Related Content Abstract Introduction Results Discussion Materials and Methods Supporting Information Acknowledgments Author Contributions References Reader Comments (0) Figures Abstract In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the “
Human intestinal microbiota composition is associated with local and systemic inflammation in obesity
Verdam, F.J. ; Fuentes Enriquez de Salamanca, S. ; Jonge, C. de; Zoetendal, E.G. ; Erbil, R. ; Greve, J.W. ; Buurman, W.A. ; Vos, W.M. de; Rensen, S.S. - \ 2013
Obesity 21 (2013)12. - ISSN 1930-7381 - p. E607 - E615.
human gut microbiota - diet-induced obesity - high-fat diet - fecal calprotectin - nonalcoholic steatohepatitis - weight-loss - bowel - mice - permeability - disease
OBJECTIVE: Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. DESIGN AND METHODS: Fecal microbiota composition of 28 subjects (BMI 18.6-60.3 kg m-2 ) was analyzed by a phylogenetic profiling microarray. Fecal calprotectin and plasma C-reactive protein levels were determined to evaluate intestinal and systemic inflammation. Furthermore, HbA1c , and plasma levels of transaminases and lipids were analyzed. Gastroduodenal, small intestinal, and colonic permeability were assessed by a multisaccharide test. RESULTS: Based on microbiota composition, the study population segregated into two clusters with predominantly obese (15/19) or exclusively nonobese (9/9) subjects. Whereas intestinal permeability did not differ between clusters, the obese cluster showed reduced bacterial diversity, a decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of potential proinflammatory Proteobacteria. Interestingly, fecal calprotectin was only detectable in subjects within the obese microbiota cluster (n = 8/19, P = 0.02). Plasma C-reactive protein was also increased in these subjects (P = 0.0005), and correlated with the Bacteroidetes/Firmicutes ratio (rs = -0.41, P = 0.03). CONCLUSIONS: Intestinal microbiota alterations in obese subjects are associated with local and systemic inflammation, suggesting that the obesity-related microbiota composition has a proinflammatory effect
Dietary Protein Affects Gene Expression and Prevents Lipid Accumulation in the Liver in Mice
Schwarz, J. ; Tome, D.G. ; Baars, A. ; Hooiveld, G.J.E.J. ; Müller, M.R. - \ 2012
PLoS ONE 7 (2012)10. - ISSN 1932-6203
high-fat diet - insulin-resistance - hepatic steatosis - physical-activity - adipose-tissue - body-weight - life-style - disease - rats - profiles
Background and Aims: High protein (HP) diets are suggested to positively modulate obesity and associated increased prevalence of non-alcoholic fatty liver (NAFLD) disease in humans and rodents. The aim of our study was to detect mechanisms by which a HP diet affects hepatic lipid accumulation. Methods: To investigate the acute and long term effect of high protein ingestion on hepatic lipid accumulation under both low and high fat (HF) conditions, mice were fed combinations of high (35 energy%) or low (10 energy%) fat and high (50 energy%) or normal (15 energy%) protein diets for 1 or 12 weeks. Effects on body composition, liver fat, VLDL production rate and the hepatic transcriptome were investigated. Results: Mice fed the HP diets displayed a lower body weight, developed less adiposity and decreased hepatic lipid accumulation, which could be attributed to a combination of several processes. Next to an increased hepatic VLDL production rate, increased energy utilisation due to enhanced protein catabolic processes, such as transamination, TCA cycle and oxidative phosphorylation was found upon high protein ingestion. Conclusion: Feeding a HP diet prevented the development of NAFLD by enhancing lipid secretion into VLDL particles and a less efficient use of ingested calories.
Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance
Hoeks, J. ; Herpen, N.A. ; Mensink, M.R. ; Moonen-Kornips, E. ; Beurden, D. van; Hesselink, M.K.C. ; Schrauwen, P. - \ 2010
Diabetes 59 (2010)9. - ISSN 0012-1797 - p. 2117 - 2125.
intramyocellular lipid-content - receptor-gamma coactivator-1 - type-2 diabetic-patients - physically fit men - high-fat diet - uncoupling protein-3 - substrate oxidation - atp synthesis - respiration - expression
OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS-While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS-Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS-These findings confirm that the insulin-resistant State has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. Diabetes 59: 2117-2125, 2010
Appetite control: methodological aspects of the evaluation of foods
Blundell, J.E. ; Graaf, C. de; Hulshof, T. ; Jebb, S.A. ; Livingstone, B. ; Lluch, A. ; Mela, D.J. ; Salah, S. ; Schuring, E. ; Knaap, H.C.M. van der; Westerterp, M. - \ 2010
Obesity Reviews 11 (2010)3. - ISSN 1467-7881 - p. 251 - 270.
sensory-specific satiety - high-fat diet - energy-intake - high-carbohydrate - ad-libitum - base-line - body-weight - individual variability - macronutrient intake - covert manipulation
This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.
Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reproduction study in Wistar rats
Ven, L.T.M. van der; Kuil, T. van de; Leonards, P.E.G. ; Slob, W. ; Lilienthal, H. ; Litens, S. ; Herlin, M. ; Hakansson, H. ; Canton, R.F. ; Berg, M. ; Visser, T.J. ; Loveren, H. van; Vos, J.G. ; Piersma, A.H. - \ 2009
Toxicology Letters 185 (2009)1. - ISSN 0378-4274 - p. 51 - 62.
brominated flame retardants - high-fat diet - sprague-dawley rats - oral dose toxicity - response elements - thyroid-hormone - breast-milk - inner-ear - flutamide - retinoids
The brominated flame retardant (BFR) hexabromocyclododecane was tested in a one-generation reproduction assay in Wistar rats, enhanced for endocrine parameters. A solution of the compound in corn oil was mixed in the feed, targeting at dietary exposure of 0-0.1-0.3-1-3-10-30-100 mg/kg body weight/day (mkd) in parental rats during 10 (males) or 2 (females) weeks premating, during gestation and lactation, and in their F1 offspring from weaning until final necropsy. Effects were assessed in F1 animals. Livers of these animals showed increased HBCD concentrations, in a dose-dependent way. The trabecular bone mineral density of the tibia was dose-dependently decreased in females (BenchMark Dose Lower confidence bound, BMDL = 0.056 mkd). The IgG response after immunization with sheep red blood cells (SRBC) was increased in males (BMDL = 0.46 mkd). Further sensitive effects were decreased weight of the testis (BMDL = 1.5 mkd), increased fraction of neutrophilic granulocytes (BMDL = 7.7 mkd), decreased concentration of apolar retinoids in female livers (BMDL = 1.3 mkd), and decreased plasma alkaline phosphatase in females (BMDL = 8.6 mkd). CYP19/aromatase activity in the ovary was correlated to the concentration of gamma-HBCD in the liver. A developmental origin of these effects is considered, and this is also true for sensitive effects observed in neurobehavioural testing in littermates from the same experiment, i.e. in the brain-stem auditory evoked potentials and in a catalepsy test [Lilienthal, H., Van der Ven, L.T.M., Piersma, A.H., Vos, J.G. Neurobehavioral effects of the brominated flame retardant hexabromocyclododecane (HBCD) in rats after pre- and postnatal exposure, in press]. The low BMDLs of these effects may raise concern for human health, particularly when based on body burdens of HBCD, which leads to critical margins of exposure particularly for the occupational setting
Exploration of PPAR functions by microarray technology: A paradigm for nutrigenomics
Bünger, M. ; Hooiveld, G.J.E.J. ; Kersten, A.H. ; Müller, M.R. - \ 2007
Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids 1771 (2007)8. - ISSN 1388-1981 - p. 1046 - 1064.
activated-receptor-alpha - gene-expression profiles - high-fat diet - target genes - mouse-liver - nuclear receptors - agonist ciprofibrate - gamma overexpression - cellular plasticity - metabolic syndrome
Traditionally, nutritional science was mainly concentrated on nutrient deficiencies and their effects on health and disease. However, over the past few decades, research emphasis has gradually shifted to the link between (over)-nutrition and chronic diseases. Driven by the continuing and accelerating discoveries in omics technology, unique possibilities have emerged to investigate the genome-wide effects of nutrients at the molecular level. Nutrigenomics uses these techniques in combination with a range of models and molecular tools as a strategy to understand the mechanistic basis of nutrition. As a paradigm for this strategy microarray analysis of genes regulated by peroxisome proliferator-activated receptors (PPARs) can serve. PPARs are ligand-activated transcription factors mediating the effect of unsaturated fatty acids and certain drugs on gene expression. Physiologically they act as fatty acid sensors in metabolic active organs, regulating a wide range of metabolic and signaling pathways. This allows cells to modulate their function and metabolic capacity, for example according to diet/nutrient-related changes in ligand concentration. Although much is already known about PPARs, gaps in our knowledge remain. In so far as the biological role of a particular PPAR is directly coupled to the function of its target genes, probing PPAR-regulated genes via the application of genomics tools can greatly improve our understanding of PPAR function. In this review we summarize and discuss the application of transcriptomics to study PPAR function, and discuss some of the challenges inherent to the application of transcriptomics to nutrigenomics research.