Project description:High fat diet (HFD), if prolonged, leads to obesity thereby accelerating the development of many ageing-related pathologies including chronic inflammation, cardiovascular disease, diabetes, and a higher predisposition to develop cancer. We asked whether HFD could reprogram the circadian output of young stem cells in a manner similar to what we observed during physiological ageing. HFD has been recently shown to induce a rewiring of the liver circadian transcriptome and metabolome, although in an obesity-independent manner. We therefore fed young (8 week old) C57Bl6 mice with HFD or its control diet for 7-weeks, a time when mice had not yet become obese, and performed circadian transcriptome analysis.
Project description:High fat diet (HFD), if prolonged, leads to obesity thereby accelerating the development of many ageing-related pathologies including chronic inflammation, cardiovascular disease, diabetes, and a higher predisposition to develop cancer. We asked whether HFD could reprogram the circadian output of young stem cells in a manner similar to what we observed during physiological ageing. HFD has been recently shown to induce a rewiring of the liver circadian transcriptome and metabolome, although in an obesity-independent manner. We therefore fed young (8 week old) C57Bl6 mice with HFD or its control diet for 7-weeks, a time when mice had not yet become obese, and performed circadian transcriptome analysis.
Project description:We compared the transcriptome of Suprachiasmatic Nucleus in C57BL/6J mice fed a high-fat diet or normal chow through an entire circadian cycle: 6 time points (TP) every four hours.
Project description:The popularity of high fat foods in modern society has been associated with epidemic of various metabolic diseases characterized by insulin resistance, the pathology of which involves complex interactions between multiple tissues such as liver, skeletal muscle and white adipose tissue (WAT). To uncover the mechanism by which excessive fat impairs insulin sensitivity, we conducted a multi- tissue study by using TMT-based quantitative proteomics. 3-week-old ICR mice were fed with high fat diet (HFD) for 19 weeks to induce insulin resistance. Liver, skeletal muscle and epididymal fat were collected for proteomics screening. Additionally, PRM was used for validating adipose differential proteins. By comparing tissue-specific protein profiles of HFD mice, multi-tissue regulation of glucose and lipid homeostasis and corresponding underlying mechanisms was systematically investigated and characterized. NC: normal birth weight + chow diet; NH: normal birth weight + high fat diet; LC: low birth weight + chow diet; LH: low birth weight + high fat diet.
Project description:The pattern of gene expression changes were analyzed in the skeletal muscle of knock-in mouse models of SBMA fed either a normal chow diet (NCD) or a high-fat diet (HFD).
Project description:Mice which lack transcriptional corepressor RIP140 show muscle fibre-type switching and increased metabolic gene expression. Comparison between skeletal muscle tissue from wild type and RIP140-null mice fed normal or high-fat diet. Switched the diet when mice were 1 month old, then sampled at 3 months.
Project description:Objective Improving mitochondrial function is a promising strategy for intervention in type 2 diabetes mellitus. This study investigated the preventive effects of sodium ferrous citrate (SFC) and 5-aminolevulinic acid phosphate (ALA) on several metabolic dysfunctions associated with obesity because they have been shown to alleviate abnormal glucose metabolism in humans. Methods Six-week-old male C57BL/6J mice were fed with a normal diet, a high-fat diet, or a high-fat diet supplemented with SFC and ALA for 15 weeks. Results The simultaneous supplementation of SFC + ALA to high-fat diet-fed mice prevented loss of muscle mass, improved muscle strength, and reduced obesity and insulin resistance. SFC + ALA prevented abnormalities in mitochondrial morphology and reverted the diet effect on the skeletal muscle transcriptome, including the expression of glucose uptake and mitochondrial oxidative phosphorylation-related genes. In addition, SFC + ALA prevented the decline in mitochondrial DNA copy number by enhancing mitochondrial DNA maintenance and antioxidant transcription activity, both of which are impaired in high-fat diet-fed mice during long-term fasting. Conclusions These findings suggest that SFC + ALA supplementation exerts its preventive effects in type 2 diabetes mellitus via improved skeletal muscle and mitochondrial health, further validating its application as a promising strategy for the prevention of obesity-induced metabolic disorders.
Project description:Circadian and metabolic processes are codependent. This experiment was designed to understand how a high fat diet affects circadian gene expression in the liver. Circadian gene expression in the liver is necessary for energy balance. Animals consuming normal chow or high fat diet (60% kcal from fat) for ten weeks were analyzed for circadian gene expression. Livers were harvested from animals every four hours throughout the circadian cycle.
Project description:Core diet-induced obesity networks were constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet responsive genes identified in liver by time-course microarray analysis (8 time-points over 24 weeks) of high-fat diet fed mice compared to normal diet fed mice. IPA identified five core diet-induced obesity networks with time-dependent gene expression changes in liver. When we merged core diet-induced obesity networks, Tlr2, Cd14 and Ccnd1 emerged as hub genes associated with both liver steatosis and inflammation and were altered in a time-dependent manner. Further protein-protein interaction network analysis revealed Tlr2, Cd14 and Ccnd1 were inter-related through the ErbB/insulin signaling pathway. Dynamic changes occur in molecular networks underlying diet-induced obesity. Tlr2, Cd14 and Ccnd1 appear to be hub genes integrating molecular interactions associated with the development of NASH. Therapeutics targeting hub genes and core diet-induced obesity networks may help ameliorate diet-induced obesity and NASH. Total RNA obtained from isolated liver of C57BL/6J mice fed normal diet or high fat diet for 0, 2, 4, 6, 8, 12, 16, 20 and 24 weeks.
