Project description:Retrobulbar fat deposits surround the posterior retina and optic nerve head, but their function and origin are obscure. We report that mouse retrobulbar fat is a neural crest-derived tissue histologically and transcriptionally resembles interscapular brown fat. In contrast, human retrobulbar fat closely resembles white adipose tissue. Retrobulbar fat is also brown in other rodents, which are typically housed at temperatures below thermoneutrality, but is white in larger animals. We show that retrobulbar fat in mice housed at thermoneutral temperature show reduced expression of the brown fat marker Ucp1, and histological properties intermediate between white and brown fat. We conclude that retrobulbar fat can potentially serve as a site of active thermogenesis, that this capability is both temperature and species-dependent, and that this may facilitate regulation of intraocular temperature.
Project description:Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in human primary adipose-derived stromal-vascular cells differentiated into adipocytes. However, the permissiveness to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Cells of visceral adipose tissue origin express more ACE2 and are more permissive to SARS-CoV-2 infection than their subcutaneous counterpart. SARS-CoV-2 infection leads to inhibition of lipolysis in cells of subcutaneous origin, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral adipose tissue cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human adipose tissue cells, replicating and altering cell function and viability in a fat depot- and viral lineage-dependent fashion.
Project description:We investigated gene expression signatures in subcutaneous inguinal adipose tissue obtained from wild type and R6/2 mice with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD. Gene expression was assessed using Affymetrix GeneChip® Mouse Gene 2.0 ST Array. Target genes were technically validated using real-time quantitative PCR. 12 subcutaneous inguinal white adipose tissue samples were analyzed by affymetrix: 6 wild-type samples; 6 R6/2 mouse samples.
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: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: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: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:Adipose tissue is the major depot for energy storage. Recent studies have shown that at least three types of adipocytes can be distinguished depending on their anatomical locations : 1) The classic brown adipocytes, i.e., brown adipose tissue (BAT); 2) The 'brite' (brown-in-white) adipocytes, i.e. inguinal white adipose tissue (iWAT); 3) The 'true' white adipocytes, i.e., epididymal white adipose tissue (eWAT). Two strains of mice (SV129 and C57BL/6J) were used in this study. SV strain is resistant to obesity and latter is prone to obesity. Pre-adipocyte cells were isolated from subcutaneous tissue (iWAT) to create four groups of cell cultures per strain of mouse.
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.
