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:To understand differences in microRNA (miRNA) signatures between two different diets with and without EPA in brown, subcutaneous, and viscerl tissue from C57BL/6 mice to understand mechanistic insight regarding their contribution to metabolic disorders in obesity. We performed small RNA-sequencing of brown, subcutaneous adipose from high fat diet (45% kcal from fat) and high fat diet supplemented with EPA (45% Kcal from fat, 6.75% EPA). Using the Gunaratne Next Generation pipeline (published in Creighton et al. 2009) miRNA expression profiles were identified. Counts of each unique read were normalized to total usable reads, and had 40 counts added. We mapped about 13.8 million sequence reads per sample to the Mus musculus genome (build mm 10). AS a total 1251 miRNAs were identified in three adipose tissue and out of which in bown adipose tissue 15 showd differential expression between BF-HF and BF-EPA .IN subcutaneous adipose tissue 3 miRNAs showed differntial expression between SUB-HF and SUB-EPA. EPA differentially regulate specific miRNAs expression in brown, subcutaneous, and visceral adipose tissue.
Project description:We identified differentially expressed genes in epididymal white adipose tissue of high fat diet(HFD)-fed mice compared to low fat diet-fed mice using microarray analysis. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity, and skeletal system development were downregulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodeling, and inflammation were upregulated. The top 10 up- or downregulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1, and Gpnmb, whose roles in obesity-associated adipose tissue deterioration are poorly understood. Total RNA of epididymal white adipose tissue was obtained from low fat diet (10 kcal% fat)- and high fat diet(45 kcal% fat)-fed mice and mRNA expression was measured using microarray analysis.
Project description:Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from the development of inflammation and obesity under normal feeding conditions, and the progression to metabolic dysfunction under dietary stress. Genetic ablation of SIRT1 from adipose tissue leads to gene expression changes that highly overlap with changes induced by high fat diet in wild type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high fat diet induces the cleavage of SIRT1 in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction. Four replicates from four different biological conditions: 1) SIRT1 wild-type fed low fat diet, 2) SIRT1 wild-type fed high fat diet, 3) SIRT1 knock-out fed low fat diet, 4) SIRT1 knock-out fed high fat diet
Project description:This project includes proteomic data of brown adipose tissue from high-fat diet-induced obese mice versus wild-type mice. WTB reprents the brown adipose tissue from wild-type mice.DIOB reprents the brown adipose tissue from diet-induced obesity mice.
Project description:This project includes proteomic data of inguinal white adipose tissue from high-fat diet-induced obese mice versus wild-type mice. WTi reprents the inguinal white adipose tissue from wild-type mice.DIOi reprents the inguinal white adipose tissue from diet-induced obesity mice.
Project description:Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell–deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue–resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue–resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance. four samples
Project description:The effect of dietary calcium and dairy proteins on adipose tissue gene expression profile in diet induced obesity Experiment Overall Design: 9-week-old C57Bl/6J-mice were divided into two groups (n=10/group). The control diet was a standard high-fat diet (60% of energy) low in calcium (0.4%). The whey protein diet was a high-calcium (1.8%) high-fat diet with whey protein isolate. After the 21-week treatment, the adipose tissue transcript profiling (2 mice/group) was carried out using Affymetrix Mouse Genome 430 2.0 array.
