Transcriptomic profiling of differentially expressed mRNA, lncRNA and circRNA in lean and obese individuals
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE235696 | GEO | 2023/09/13
REPOSITORIES: GEO
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Project description:Long non-coding RNAs (lncRNAs) belong to a recently discovered class of molecules proposed to regulate various cellular processes. Here, we systematically analyzed their expression in human subcutaneous white adipose tissue (WAT) and found that a limited set was differentially expressed in either obesity or the insulin resistance that usually follows obesity. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs 1(ASMER-1) and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1or ASMER-2 by antisense oligonucleotides using in vitro differentiated human adipocytes altered lipolysis and adiponectin secretion, respectively. The observed effects could be attributed to changes in the expression of genes controlling inflammation and lipid metabolism. Our data demonstrate that lncRNAs are modulators of the metabolic and endocrine functions in fat cells and also provide an emerging link between WAT and common metabolic conditions.
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Project description:Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders. We used microarrays to identify global gene expression in 3T3-L1 adipocytes lacking TBLR1 and compared gene expression to control shRNA treated cells in both basal and isoproterenol stimulated states.
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