Project description:C57Bl6/J male mice were put on different diets at 5 weeks of age, with a standard diet (SD) or a High-Fat High-Sucrose Diet (HFHS) or a Choline-Deficient High-Fat Diet (CDHFD) during 6 months. Primary hepatocytes cultures from 3 different models were synchronized in the cell cycle. Transcriptomic analysis was perfomed at 48hours of culture when HFHS and CDHFD hepatocytes harbor replication stress.
Project description:mir342-/- and mir342wt/wt C57BL/6J mice were fed with standard diet (STD) and high fat-high sucrose diet (HFHS). We used microarrays to investigate the mRNA expression profile in the epididymal adipose tissues.
Project description:To determine CREBH-mediated hepatic gene expression changes in hifh-fat high-sucrose (HFHS) dit feeding, we employed the microarray analysis. We collected the livers from male WT and CREBH-Tg mice fed with HFHS diet for 12 weeks from 6 weeks old.
Project description:mir221/222 AdipoKO and mir221/222 flox/y C57BL/6J mice were fed with standard diet (STD) and high fat-high sucrose diet (HFHS). We used microarrays to investigate the mRNA expression profile in the epididymal adipose tissues.
Project description:There is growing evidence that energy metabolism and insulin action are regulated by mechanisms that follow a diurnal rhythm and it has been proposed that defects in Akt signalling are associated with the pathophysiology of metabolic disease. It is therefore important to investigate these parameters under physiology of the free-living state. We therefore examined the insulin action in muscle of chow or high fat, high sucrose diet-fed (HFHS) rats during the normal diurnal cycle. HFHS animals displayed hyperinsulinemia, however had reduced systemic glucose disposal and impaired muscle glucose uptake during the feeding period. Proteomics and phosphoproteomics was performed over the diurnal cycle in chow and HFHS rats.
Project description:We have employed whole genome microarray expression profiling in the liver of mice fed a high-fat, high-sucrose diet for 15 weeks to search genes with N-terminal signal sequences whose expression is altered concomitantly with changes in islet size. At 15 weeks, this analysis revealed a significant >4-fold upregulation in 118 genes and downregulation by >75% in 22 genes encoding putative secreted factors in liver of mice fed a HFHS, although few changes (<2-fold upregulated or >one-half downregulated) were observed at 10 weeks. Expression of four genes (NRG1, GPNMB, SERPINB1 and HGF) from this signature was quantified in the different RNA samples by real-time PCR, confirming low variability between mice.
Project description:Oral consumption of histidyl dipeptides such as l-carnosine has been suggested to promote cardiometabolic health, although therapeutic mechanisms remain incompletely understood. We recently reported that oral consumption of a carnosine analog suppressed markers of fibrosis in liver of obese mice, but whether antifibrotic effects of carnosine extend to the heart is not known, nor are the mechanisms by which carnosine is acting. Here, we investigated whether oral carnosine was able to mitigate the adverse cardiac remodeling associated with diet induced obesity in a mouse model of enhanced lipid peroxidation (i.e., glutathione peroxidase 4 deficient mice, GPx4+/−), a model which mimics many of the pathophysiological aspects of metabolic syndrome and T2 diabetes in humans. Wild-type (WT) and GPx4+/− male mice were randomly fed a standard (CNTL) or high fat high sucrose diet (HFHS) for 16 weeks. Seven weeks after starting the diet, a subset of the HFHS mice received carnosine (80 mM) in their drinking water for duration of the study. Carnosine treatment led to a moderate improvement in glycemic control in WT and GPx4+/− mice on HFHS diet, although insulin sensitivity was largely unchanged. Interestingly, while our transcriptomic analysis revealed that carnosine therapy had no significant impact on global gene expression in the heart, carnosine substantially upregulated cardiac GPx4 expression in both WT and GPx4+/− mice on HFHS diet. Carnosine also significantly reduced protein carbonyls and iron levels in myocardial tissue from both genotypes on HFHS diet. Importantly, we observed a robust antifibrotic effect of carnosine therapy in hearts from mice on HFHS diet, which further in vitro experiments suggest is due to carnosine’s ability to suppress collagen-cross-linking. Collectively, this study reveals antifibrotic potential of carnosine in the heart with obesity and illustrates key mechanisms by which it may be acting.
Project description:Metabolic syndrome (MetS) is a complex disorder with multidimensional etiology that encompasses diverse symptoms such as hyperlipidemia, abdominal obesity, and insulin resistance. Western diets such as the high fat high sucrose diet (HFHS) and those high in fructose ave been associated with increased prevalence of MetS. Despite the fact that various metabolic tissues have been implicated in MetS pathogenesis, the role of individual cell types embedded in these tissues has yet to be elucidated. To address this, we performed single cell RNA sequencing to examine thousands of individual cells from the hypothalamus, liver, adipose, and small intestine from both HFHS- and fructose-induced MetS mouse models. We found differential sensitivity of responsive cell types, genes, and pathways between HFHS and fructose diets, with hypothalamic neurons particularly sensitive to the high fructose diet and adipose progenitor cells particularly sensitive to HFHS diet. Network analysis identified both known (Avp, Apoe, C3) and novel ligands (Gal and Fga) that mediate ligand-receptor crosstalk between tissues in MetS. The identification of major cell types, molecular pathways, and regulators of MetS induced by different risk diets facilitates precision treatment of MetS subtypes.