Project description:We set two groups of 2-month-old C57BL6/J male mice at either thermoneutral temperature of 30℃ or under cold stimulation at 4℃ for one week. To identify events vital to beige fat activation, we performed RNA-seq using mice subcutaneous adipose tissue (iWAT) and focused on differentially-expressed genes characterized significant upregulation.
Project description:We set two groups of 2-month-old C57BL6/J male mice at either thermoneutral temperature of 30℃ or under cold stimulation at 4℃ for one week. To identify events vital to beige fat activation, we performed MeRIP-seq using mice subcutaneous adipose tissue (iWAT) and focused on differentially-expressed genes characterized significant upregulation.
Project description:Beige adipocytes are newly identified thermogenic-poised adipocytes that could be activated by cold or β3-adrenergic receptor (β3-AR) signaling and offer therapeutic potential for treating obesity and metabolic diseases. Here we applied RNA-sequencing analysis in the beige fat of mice under cold exposure or β3-AR agonist CL316,243 (CL) treatment to provide a comparative and comprehensive analysis for the similarity and heterogeneity of these two stimulants. Importantly, via KEGG analysis, we found that cold and CL commonly induced oxidative phosphorylation. Meanwhile, cold increased glycerolipid and amino acids metabolism while CL treatment triggered a broader spectrum of metabolic responses including carbohydrate metabolism. Besides, cold or CL treatment featured greater heterogeneity in downregulated gene programs. Of note, the top changed genes in each category were confirmed by qPCR analysis. Overall, our analysis provided a better understanding of the heterogeneity of differential models for beige adipocytes activation and a possible clue for optimizing β3-AR agonists in the future.
Project description:Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
