Project description:Obesity results from a chronic imbalance between energy intake and energy expenditure, with excess calories stored as fat. As such, weight loss has long been considered as a primary goal of treatment for obesity. A surgical treatment of severe obesity such as gastric bypass provides the most dramatic reductions in body weight, and a well-known effect of weight loss is an improvement in insulin sensitivity. However, the molecular mechanism underlying this association remains unclear. Thus, we profiled skeletal muscle of morbidly obese patients before and after gastric bypass surgery. Results from this project will provide global patterns of gene expression with weight loss, which help to understand the pathogenesis of obesity at the molecular level. Experiment Overall Design: To identify responsive genes to weight loss.
Project description:Obesity results from a chronic imbalance between energy intake and energy expenditure, with excess calories stored as fat. As such, weight loss has long been considered as a primary goal of treatment for obesity. A surgical treatment of severe obesity such as gastric bypass provides the most dramatic reductions in body weight, and a well-known effect of weight loss is an improvement in insulin sensitivity. However, the molecular mechanism underlying this association remains unclear. Thus, we profiled skeletal muscle of morbidly obese patients before and after gastric bypass surgery. Results from this project will provide global patterns of gene expression with weight loss, which help to understand the pathogenesis of obesity at the molecular level. Keywords: Time-Series
Project description:Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy men ingested saturated (SFA) or poly unsaturated (PUFA) fat-rich diets for six weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with PUFA. In mice, eucaloric feeding of human PUFA and SFA diets lowered hepatic triacylglycerol content compared to low-fat fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.
Project description:Low-carbohydrate, high-fat diets under eucaloric conditions are associated with several health-beneficial metabolic effects in humans, particularly in the liver. We recently observed that apolipoprotein A-IV (apoA-IV), a highly abundant apolipoprotein, was among the most upregulated proteins in the circulation after six weeks of high fat intake in humans. However, the dietary regulation of apoA-IV and the potential effects of apoA-IV on regulation of glucose- and lipid metabolism remain to be fully established. We here demonstrate in healthy human individuals that both short- and long-term high-fat intake increased fasting plasma apoA-IV concentrations by up to 54%, while high carbohydrate intake suppressed plasma apoA-IV concentrations. In mice, administration of apoA-IV acutely lowered blood glucose levels in lean and obese mice. Interestingly, this was related to a dual mechanism, involving both inhibition of hepatic glucose production and increased glucose uptake into white and brown adipose tissues. In addition to an effect on hepatic glucose production, the apoA-IV-induced liver proteome revealed increased capacity for lipoprotein clearance. The effects of apoA-IV in the liver and adipose tissues were obtained concomitant with increased whole-body fatty acid oxidation. Upon glucose stimulation, an improvement in glucose tolerance by apoA-IV administration was related to potentiation of glucose-induced insulin secretion, while apoA-IV inhibited glucagon secretion ex vivo in islets. In conclusion, we find that ApoA-IV is potently increased by the intake of fat in humans, and that several beneficial metabolic effects, previously associated with high fat intake in humans, are mimicked by administration of apoA-IV protein to mice.
Project description:This study used untargeted proteomics to compare blood proteomic profiles in two groups of adults that differed widely in lifestyle habits. The goal was to identify a core list of proteins that were either upregulated or downregulated based on adherence to recommended lifestyle habits in adults. A total of 52 subjects in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females) participated in this cross-sectional study. Age, education level, marital status, and height did not differ significantly between LIFE and CON groups. The LIFE and CON groups differed markedly in body composition and fat mass-related anthropometric measurements including waist circumference, body mass index (BMI), sagittal abdominal diameter (SAD), and body composition (body fat percentage and fat mass index or FMI) (p<0.001). LIFE and CON groups were also widely disparate in physical activity patterns and maximal aerobic fitness, dietary intake patterns, disease risk factor prevalence, blood measures of inflammation, triglycerides, HDL-cholesterol, glucose, and insulin, weight-adjusted leg/back and handgrip strength, and mood states. The proteomics analysis showed strong group differences for 39 of 725 proteins identified in the dried blood spot samples. Of these, 18 were downregulated in the LIFE group and collectively indicated a lower innate immune activation signature. A total of 21 proteins were upregulated in the LIFE group and supported greater lipoprotein metabolism and HDL remodeling. Lifestyle-related habits and biomarkers were probed and the variance (>50%) in downregulated and upregulated proteins was best explained by group contrasts in indicators of body composition and visceral fat including FMI and SAD. This cross-sectional study established that a relatively small number of upregulated and downregulated proteins are associated with good lifestyle habits. A targeted “lifestyle” proteomic panel based on these data could be used in future studies to determine the efficacy of various prevention and treatment strategies.
Project description:Exogenous glucocorticoids regulate the muscl-fat axis communication, but little attention is paid to their frequency of intake. Here we investigated the transcriptional effects of prednisone in muscle and adipose tissue when dosed as intermittent once-weekly 1mg/kg i.p. versus once-daily 1mg/kg in WT obese mice. Prior to treatment, mice were fed a high-fat diet for 12 weeks. After 12 weeks of treatment, we performed RNA-seq analysis in muscle (quadriceps) and white adipose tissue (ventral fat pad) to quantitate gene expression at isoform level.
Project description:We used Affymetrix microarrays to investigate gene expression changes in PBMNCs isolated from female and male pigs to determine significant modulatory effects that may have been induced by the intake of GE and (or) RES during 4 months in animals fed an atherogenic diet (AD) . The aim of this work was to determine whether the intake of low doses of a Grape Extract (GE; 1 g/70 Kg animal body weight) and (or) Resveratrol (RES; 18 mg/70 Kg animal body weight) exerted any modulatory effects, at the level of gene expression, in PBMNCs isolated from female and male pigs exposed to an atherogenic diet (AD) for 4 months. We isolated PBMNCs, and the corresponding total RNA, from 2 female and 2 male pigs for each group. Pure RNA was extracted from the PBMNCs for microarrays analyses (Affymetrix) and gene differential expression determined between the AD fed animals and control (CT) animals (to determine the effects of a high-fat consumption) and between the AD fed animals supplemented with GE and (or) RES and the animals fed the AD diet alone (to determine the effects of GE and (or) RES on the fat consumption). In addition, the effects of the consumption of GE and RES against a standard control diet (CT) were also determined. Differential gene expression: 1) AD vs CT (response to exposure to a high-fat diet); 2) AD-GE vs AD (modulatory effects of the intake of a grape extract on high-fat fed animals); 3) AD-GE-RES vs AD (modulatory effects of the intake of a resveratrol-enriched grape extract on high-fat fed animals); 4) AD-RES vs AD (modulatory effects of the intake of resveratrol on high-fat fed animals); 5) CT-GE-RES vs CT (modulatory effects of the intake of a resveratrol-enriched grape extract on animals fes a standard pig chow).
Project description:Background: The age-related loss of muscle mass significantly contributes to the development of chronic diseases, loss of mobility and dependency on others, yet could be improved by an optimized lifestyle. Objective: The goal of this randomized controlled trial was to compare the influence of a habitual diet (CON) with either a diet containing the recommended protein intake (RP) or a high protein intake (HP), both with and without strength training, on the plasma proteome in older adults. Methods: 136 women and men (65-85 years) were randomly assigned to three intervention groups. CON continued their habitual diet; participants of the HP and RP group consumed either high protein or standard foods. After 6 weeks of dietary intervention, HP and RP groups additionally started a strength training intervention twice per week for 8 weeks. 24h dietary recalls were performed every 7 to 10 days. Body composition was assessed and blood taken. Plasma proteomics were assessed with LC-MS. Results: Participants of the HP group doubled their baseline protein intake from 0.80±0.31 g/kg BW/d to 1.63±0.36 g/kg BW/d; RP increased the protein intake from 0.89±0.28 g/kg BW/d to 1.06±0.26 g/kg BW/d. The CON group kept the protein intake stable throughout the study. Combined exercise and HP initiated notable changes, resulting in a reduction in bodyfat and increased muscle mass. Proteomics analyses revealed 14 significantly affected proteins by HP diet, regulating innate immune system, lipid transport and blood coagulation, yet the additional strength training did not elicit further changes. Conclusions: Combined HP and resistance exercise in healthy older adults seem to induce favorable changes in the body composition. Changes in the plasma proteome due to the high protein diet point to a beneficial impact for the innate immune system, lipid transport and blood coagulation system, all of which are involved in chronic disease development.
Project description:Exposure to chronic heat stress not only reduces body weight gain in growing broilers, but also enhances fat deposition in the abdomen, subcutaneous, and intramuscular. To elucidate this phenomenon, numerous studies have examined changes in the transcripts, protein, and metabolic levels in the liver, the primary site of de novo fat synthesis in birds. On the other hand, changes in adipose tissue, the direct site of fat deposition, have not been unclear. To elucidate the changes in adipose tissue of chickens heat-exposure, we demonstrated the experiments rearing chickens in a heat environment (32°C) for 14 days, and then compared with the control group that reared in thermoneutral condition (22°C), and a pair-fed groups that reared in thermoneutral condition but feed intake was limited to the same levels as that in the heat-exposed group. Despite the feed intake was equal to that of the pair-fed group, the ratio of abdominal fat to body weight in the heat-exposed group was maintained at the same level as that in the control group. In addition, the heat-exposed group showed a significant decrease in the concentration of free fatty acids in plasma compared with the other 2 groups. Transcriptome analysis of abdominal fat between the heat-exposed and control groups revealed 459 differentially expressed genes were indicated. Notably, in heat-exposed group, the expression of genes related to lipid synthesis increased in adipose tissue compared with control group. Taken together, these results indicate that chronic heat has a lipid-deposition-promoting effect on growing broiler chicken adipose tissue
Project description:Roux-en-Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a ~20% failure rate. We used our established RYGB model in diet-induced obese (DIO) Sprague-Dawley rats, which reproduces human bi-phasic body weight (BW) loss pattern, to determine mechanisms contributing to success (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham operated Obese, and sham operated obese pair fed-linked to RYGB (PF) groups. BW, caloric intake (CI) and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphologic changes were determined. Gut, adipose and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle, expression of energy-related hypothalamic and fat peptides, receptors and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F and PF rats vs. Obese showed rapid BW decrease, followed by sustained BW loss in RYGB-S. RYGB-F and PF gradually increased BW. Expression profiling of both CNS (hypothalamus) and peripheral tissues (subcutaneous abdominal fat) strongly supported the involvement of a number of metabolic and feeding-related genes in the differential outcomes. Experiment Overall Design: 3 biological replicate RNA samples were prepared from 2 tissues (the subcutaneous abdominal fat or the hypothalamus) from rats in 3 treatment groups (rats losing weight successfully after gastric bypass surgery, rats gaining weight, and rats that were fed the same amount as the treated rats)