Long non-coding RNAs associated with metabolic traits in human white adipose tissue
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE110729 | GEO | 2021/02/14
REPOSITORIES: GEO
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Project description:The aim of this study was to identify novel long noncoding RNAs (lncRNAs) that are differentially expressed in the subcutaneous region either in obesity or insulin resistance. A number of novel lncRNAs were differentially expressed in the subcutaneous region either in obesity or insulin resistance. Two lncRNAs (termed here as adipocyte specific insulin resistance related lncRNAs (ADLNRIs), ADLNRI 1 and ADLNRI 2) were influenced by both conditions and enriched in adipocytes. Knockdown of either by antisense oligonucleotides in fat cellsadipocytes altered lipolysis and adiponectin secretion, respectively.
2018-05-23 | GSE101492 | GEO
Project description:White adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gαs- and Gαi-coupled receptors have been reported to regulate lipolysis, and Gαq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of Gα12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates Gα12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed “metabolically healthy obese” phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
2018-12-23 | GSE66131 | GEO
Project description:White adipose tissue (WAT) is a highly active metabolic and endocrine organ, and its dysfunction links obesity to a variety of diseases, ranging from type 2 diabetes to cancer. The function of WAT is under the control of multiple cell signaling systems, including that of G protein-coupled receptors (GPCRs). Gαs- and Gαi-coupled receptors have been reported to regulate lipolysis, and Gαq-coupled receptors stimulate glucose uptake in adipocytes. However, the roles of Gα12/13-coupled receptors in WAT are totally unknown. Here we show that lysophosphatidic acid receptor 4 (LPA4), an adipose cluster GPCR, selectively activates Gα12/13 proteins in adipocytes, and limits continuous remodeling and healthy expansion of WAT in mice. Under standard diet conditions, LPA4-knockout mice showed higher expression levels of mitochondrial biogenesis-related genes in WAT, along with higher production of adiponectin than control mice. In vitro studies have consistently demonstrated that the LPA4/Rho/Rho-kinase signaling pathway suppresses mRNA expression of mitochondrial biogenesis-related genes in adipocytes. In a diet-induced obesity model, LPA4-deficient mice showed “metabolically healthy obese” phenotypes, with continuous WAT expansion, and protection from WAT inflammation, hepatosteatosis, and insulin resistance. Given that GPCRs comprise the most successful class of drug targets, LPA4 would be a promising therapeutic target for obesity-related metabolic disorders.
2018-12-23 | GSE66130 | GEO
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. We analyzed 12 RNA samples extracted from 3T3-L1 adipocytes that were treated with either control or TBLR1 specific shRNAs and with or without 10 µM isoproterenol for 3 hrs. Three replicates of each condition.
2013-04-01 | E-GEOD-43658 | biostudies-arrayexpress
Project description:ApoL6 is a new LD-associated protein containing an apoprotein-like domain, expressed mainly in adipose tissue, specifically in adipocytes. ApoL6 expression is low in fasting but induced upon feeding. ApoL6 knockdown results in smaller LD with lower triglyceride (TAG) content in adipocytes, while ApoL6 overexpression causes larger LD with higher TAG content. We show that ApoL6 effect in adipocytes is by inhibition of lipolysis. While ApoL6, Perilipin 1 (Plin1) and HSL can form a complex on LD, C-terminal domain of ApoL6 directly interacts with Plin1, to compete with Plin1 binding to HSL through Plin1 N-terminal domain, thereby keeping HSL in a stand by status. Thus, ApoL6 ablation decreases WAT mass, protecting mice from diet-induced obesity, while adipose overexpression increases WAT mass to bring obesity and insulin resistance with hepatosteatosis, making ApoL6 a potential future target against obesity and diabetes.
2024-05-24 | PXD038334 | Pride
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.
2013-04-01 | GSE43658 | GEO
Project description:Enlarged white adipose tissue (WAT) is a feature of obesity and leads to changes in its paracrine and endocrine function. Dysfunction of WAT cells is associated with obesity associated disorders like type 2 diabetes and cardiovascular diseases. Resveratrol (RSV) a natural polyphenolic compound mimics beneficial effects of calorie restriction. As such, RSV seems a promising therapeutic target for obesity-associated disorders. The effect of RSV on the human adipokine profile is still elusive. Therefore, a proteomic study together with bioinformatical analysis was performed to investigate the effect of RSV on the secretion profile of mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. RSV incubation resulted in elevated basal glycerol release and reduced intracellular TG content. This increased intracellular lipolysis was accompanied by profound changes in the adipocyte secretion profile. Extracellular matrix proteins were down-regulated while processing proteins were mostly up-regulated after RSV treatment. Interestingly, RSV induced secretion of proteins protective against cellular stress and proteins involved in the regulation of apoptosis. Furthermore, we found a RSV-induced up-regulation of adiponectin and ApoE accompanied by a down-regulation of PAI-1 and PEDF secretion which may improve anti-inflammatory processes and increased insulin sensitivity. These effects are beneficial to alleviate obesity-induced metabolic complications. In addition, two novel RSV-regulated adipocyte-secreted proteins were identified.
2012-08-31 | PXD000012 | Pride
Project description:Obesity is linked to the development of metabolic disorders. Expansion of white adipose tissue (WAT) from hypertrophy of pre-existing adipocytes and/or differentiation of precursors into new mature adipocytes contributes to obesity. We found that Nck2 expression is largely restricted to WAT, raising the hypothesis that it may play a unique function in that tissue. Using mice lacking Nck2, we found that Nck2 regulates adipocyte hypertrophy thus contributing to increased adiposity and progressive glucose intolerance, insulin resistance and hepatic steatosis. These findings were recapitulated in humans such that Nck2 expression in omental WAT was inversely correlated with the degree of obesity. Mechanistically, Nck2 deficiency promoted the induction of an adipocyte differentiation program and signaling by the PERK-eIF2α-ATF4 pathway in agreement with a role for the unfolded protein response in adipogenesis. These findings uncover Nck2 as a novel regulator of adipogenesis and that perturbation in its functionality contributes to adiposity-related metabolic disorders. Differential gene expression profile between epididymal white adipose tissue of Nck2-/- and Nck2+/+ mice by RNA sequencing (Illumina HiSEq 2000)
2016-07-01 | E-GEOD-63510 | biostudies-arrayexpress
Project description:B cell-activating factor (BAFF) is critical for the survival and maturation of B2 cells. However, excess BAFF breaks the peripheral tolerance of B2-cells leading to the production of autoantibodies that cause autoimmune diseases. During obesity, BAFF is predominantly produced by white adipose tissue (WAT), and IgG autoantibodies against adipocytes are identified in the WAT of obese humans. However, it remains to be determined if the autoantibodies formed during obesity affect WAT remodeling and systemic insulin resistance. Here, we show that IgGs from high-fat diet (HFD)-induced obese mice bind to apoptotic adipocytes and promote their clearance by macrophages. Next, using murine models of obesity in which the gonadal WAT undergoes remodeling, unexpectedly we found that BAFF neutralization increased the number of dead adipocytes and exacerbated WAT inflammation and insulin resistance despite depletion of IgG autoantibodies. RNA sequencing of the stromal vascular fraction from the WAT revealed impaired B cell activation and phagocytosis pathways. In-vitro, the clearance of apoptotic adipocytes by macrophages was attenuated in the presence of IgGs from BAFF-neutralized mice compared to the control mice. Altogether, our study suggests a beneficial role of BAFF and IgG autoantibodies in WAT remodeling in obesity and the regulation of systemic insulin resistance.
2024-08-28 | GSE255950 | GEO
Project description:Purpose: To determine how STAT1 activity in white adipocytes affects insulin sensitivity. Methods: Adipocyte specific (ADIPOQ-Cre) STAT1 fl/fl mice (STAT1 fKO) and littermate controls (STAT1 fl/fl) were placed on 60% HFD for 18 weeks, followed by metabolic phenoptying and tissue harvest for RNA-seq Results: STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNg) activity enhanced insulin sensitivity in diet-induced obesity. Conclusions: Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.
2020-11-27 | GSE153337 | GEO