Project description:We have carried out whole-genome expression profiling of whole blood from obese subjects, defined as obese diet-sensitive and obese diet-resistant, and well matched lean individuals. The diet-sensitive or diet-resistant status refers to the different rates of weight loss observed in the two groups on a low-calorie diet regimen. Bioinformatic analysis revealed alterations in transcription in key pathways that are consistent with impaired capacity for fatty acid oxidation driven mitochondrial ATP synthesis in obese subjects who are resistant to weight loss. A total of 80 samples are analyzed. This consists of 20 lean subjects studied at one timepoint and 20 obese subjects (10 diet-sensitive and 10 diet-resistant) studied at 3 timepoints during caloric restriction (day of entry into program, week 3 into the program and week 6 into the program)
Project description:We used microarrays to study the gene expression dynamics during caloric restricted weight loss in obese mice after feeded with high fat diet. C57BL/6J male mice were placed on a high fat diet at 10-11 weeks of age in individual cages and kept on the diet until they reached ~ 41 g. After all the baseline (41g) measurement were made, each mouse was fed 75% of their ad libitum food intake in two divided daily "meals". The high fat diet was maintained. Mice were sacrificed after 0, 1, 3, 7, 14, 21 or 42 day of caloric restriction. Hypothalamus, liver, abdominal subcutaneous adipose, mesenteric adipose, perirenal adipose and perigonadal adipose tissues were collected for RNA extraction and hybridization on Affymetrix microarrays.
Project description:LDLR-/- mice were fed a high fat high sucrose diet with either 9,11 CLA or 10,12 CLA. Control groups included no supplementation or caloric restriction to mirror weight loss seen in CLA group. Mice were sacrificed and blood was collected into EDTA tubes. Isolated plasma was immediately frozen at -80C. Adipose tissue from gonadal fat (epididymal white adipose tissue, EWAT) and subcutaneous fat (inguinal white adipose tissue, IWAT) and liver were harvested, snap frozen in liquid nitrogen, and immediately frozen at -80C. An aliquot of thawed plasma was prepared for this project and frozen in an eppendorf tube. Small pieces of frozen tissue were cut and weighed on dry ice and packaged in individual foil packets for this project. **Note: tissue weight is approximate**
Project description:lean control, obese, and formerly obese C57BL6N mice which underwent weight loss via vertical sleeve gastrectomy or calorie restriction were injected with E0771 cells and tumor growth was monitored
Project description:We recruited ten normal-weight healthy men using inclusion criteria as previously described (Collet et al 2017). All males were healthy and not obese or overweight (average age: 23.8 years, average BMI (kg/m2): 23.3). Participants at baseline consumed a balanced diet (50% carbohydrate, 30% fat, and 20% protein). During caloric restriction, volunteers consumed 10% of normal energy requirement (226 kcal/d) for two days, again balanced (50% carbohydrate, 30% fat, and 20% protein), with the same macronutrient composition. After caloric restriction, volunteers were offered three substantial ad libitum buffet meals per day (20 MJ = 4,777 kcal) and additional snacks (16 MJ = 3,821 kcal) between meals for 2 days. They were invited to eat freely until comfortably full; food consumption was covertly measured. We collected fasting plasma samples at 0800 AM at baseline, after CR and refeeding (RF).
Project description:lean control, obese, and formerly obese C57BL6N mice which underwent weight loss via low-fat diet or various forms of calory restriction were injected with E0771 cells and tumor growth was monitored
Project description:lean control, obese, and formerly obese C57BL6N mice which underwent weight loss via low-fat diet or various forms of calory restriction were injected with E0771 cells and tumor growth was monitored
Project description:While weight loss is highly recommended for obesity, promoting inflammation resolution, >80% of those who lose weight will regain it back, resulting in worsening of disease outcomes (including cardiovascular disease), relative to never having lost weight. However, how weight loss and regain directly influence atherosclerotic inflammation was unknown and investigated in this stud. Using short-term caloric restriction (stCR) in obese mice, we found that weight loss promotes atherosclerosis resolution, independently of plasma cholesterol. Mechanistically, we found that this is partly attributed to a unique subset of macrophage, distinguished by high expression of the antibody receptor Fcgr4, that accumulated in epididymal adipose tissue and plaques with stCR and help to clear necrotic cores. Interestingly, our data suggest that eWAT-derived Fcgr4 macrophages contribute to the clearance of plaque necrotic cores. On the other hand, weight regain achieved by ab libitum feeding following the stCR phase resulted in acceleration of atherosclerosis progression and disappearance of Fcgr4 macrophages from both adipose and plaques. Furthermore, weight regain caused inflammatory reprogramming of bone marrow immune progenitors, retaining hyper-inflammatory capabilities for long periods thereafter.
Project description:We investigated the regulation of adipose tissue (AT) gene expression during different phases of a dietary weight loss program and its relationship with insulin sensitivity. Obese women followed a weight reduction program composed of an energy restriction phase (ER) with a 4-week very-low-calorie diet and a weight stabilization period (WS) composed of a 2-month low-calorie diet followed by 3 to 4 months of a weight maintenance diet. At each time point, body composition, plasma parameters and glucose disposal rate were assessed and subcutaneous AT biopsies were performed. Variations in mRNA levels were determined using DNA microarrays and reverse transcription-quantitative PCR. Distinct sets of AT genes are regulated during calorie restriction and weight stabilization revealing an unexpected temporal pattern in the link between AT and insulin sensitivity during weight loss.
Project description:Patients with heart failure with preserved ejection fraction (HFpEF) often have an unfavorable cardiometabolic profile, and obesity-related HFpEF has become a well-recognized HFpEF sub-phenotype. Targeting this unfavorable cardiometabolic profile may therefore represent a rational treatment strategy. The glucagon-like peptide-1 receptor agonist (GLP1-RA) semaglutide has been shown to induce significant weight loss and to improve cardiovascular outcomes. In this study, we investigated the cardiometabolic effects of semaglutide in a representative mouse model of HFpEF and compared it to the effects of weight loss by caloric restriction.
