Project description:Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for obesity and its associated metabolic disorders. To provide a comprehensive picture of the regulatory network in these processes, we conducted a series of transcriptome studies by RNA-seq and quantified the mRNA and lncRNA changes during white fat browning induced by chronic cold exposure, beta-adrenergic agonist and intensive exercises, brown fat activation by acute cold exposure and inactivation by thermoneutrality.
Project description:To determine the function of miR-203 in white fat browning upon cold exposure, we injected miR-203 inhibitors and negative control into inguinal white adipose tissue, followed by cold exposure (4oC) for 24 hours. Total RNA were harvested for RNA-seq.
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 found that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensible role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility for key thermogenic genes in close proximity to PPARg and EBF2 binding sites. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced 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.
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:Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue, a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPARα) in cold-induced browning. Here we aimed to investigate the importance of PPARα in driving transcriptional changes during cold-induced browning in mice. Male wildtype and PPARα−/− mice were housed at thermoneutrality (28 °C) or cold (5 °C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPARα−/− mice fasted for 24 h served as positive control for PPARα-dependent gene regulation.Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPARα−/− mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPARα genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPARα−/− mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPARα−/− mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid β-oxidation to a similar extent in wildtype and PPARα−/− mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPARα−/− mice. Finally, pharmacological PPARα activation had a minimal effect on expression of cold-induced genes in murine WAT.Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPARα, indicating that PPARα is dispensable for cold-induced browning.
Project description:Subcutaneous white adipose tissue (scWAT) is known to undergo browning in response to cold exposure. The goal of this study is to identify elusive precursors found within scWAT that possess the ability to differentiate into beige adipocytes. A single cell transcriptomics experiment conducted by us identified the tetraspanin CD81 as a marker of adipose precursor cells (APC) that can convert to beige upon cold exposure. However, what distinguishes a CD81 positive APC from its CD81 negative counterpart in the same tissue, or in a different tissue remains unknown. Therefore, we applied bulk RNA-seq to sorted populations of Lineage negative Sca1+, CD81+/ CD81- cells from subcutaneous and visceral WAT, and brown adipose tissue to decipher the molecular underpinnings that render a CD81+ APC residing in scWAT, beige in response to browning.