Metabolomics Workbench ST000675 - GNPS - Effects of rosiglitazone treatment on lipid composition
Ontology highlight
ABSTRACT:
INSTRUMENT(S): QTOF - NEGATIVE, QTOF - POSITIVE
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Maureen Kachman
PROVIDER: MSV000082717 | GNPS | Thu Aug 02 17:17:00 BST 2018
REPOSITORIES: GNPS
Similar Datasets
Project description:Reprograming of 'white' to 'brite' adipocytes with higher oxidative capacity and improved endocrine function represents a potentially important approach to address the dysfunctional adipocyte phenotypes in obesity. We find that chronic treatment with the PPAR? agonist (rosiglitazone, 1 uM for 7days in vitro) in white human adipose tissue induced metabolic changes. Our trancriptome analysis showed that higher mitochondrial and peroxisomal fatty acid oxidation pathways and other genes involved in lipid metabolism including (re)esterification are induced by rosiglitazone treatment. To understand the biochemical basis of brite vs. white human adipocytes, we will perform comprehensive metabolomic profiling of control and rosiglitazone treated tissues using unbiased lipidomics approach.
2017-06-05 | ST000675 | MetabolomicsWorkbench
Project description:The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that permanently confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity. Human pluripotent stem-cell derived mesenchymal progenitor cells (PSC-MPCs), white adipose cells (PSC-WA), and brown adipose cells (PSC-BA) were treated with DMSO (as control), a JAK3-inhibitor compound, and a SYK-inhibitor compound respectively. Transcriptomic expression profiling was performed at 24 hours and 7 days respectively. Three biological replicates are available for each condition defined by cell type, compound, and time.
2014-10-31 | E-GEOD-57896 | biostudies-arrayexpress
Project description:Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue- specific phenotypic, functional, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most pathological features were successfully reverted, we observed a high degree of metabolic dysfunction irreversibility in visceral white adipose tissue, characterised by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and apparent global phenotypic recovery, obesity specifically triggered in visceral adipose tissue a cascade of events progressing from mitochondrial metabolic and proteostatic defects to widespread cellular stress, which compromises its biosynthetic and recycling capacity. Our data indicate that obesity prompts a lasting metabolic fingerprint that leads to an aging-like progressive breakdown of metabolic plasticity in white adipose tissue. A similar phenomenon was observed in an obese human cohort following weight loss. Further human studies should help dissect patients’ stratification of this significant milestone in obesity progression.
2022-07-04 | PXD025503 | Pride
Project description:Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here, we report that IL-37, a newly-described antiinflammatory member of the IL-1 family, affects obesity-induced inflammation and insulin resistance. IL-37 transgenic mice (IL-37tg) did not develop an obese phenotype in response to a high-fat diet (HFD). Unlike WT mice, IL-37tg mice exhibited reduced numbers of adipose tissue macrophages and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. A short-term HFD intervention revealed that the IL-37-mediated improvement in glucose tolerance is independent of bodyweight. IL-37tg mice manifested a beneficial metabolic profile with higher circulating levels of the anti-inflammatory adipokine adiponectin. In vitro treatment of differentiating adipocytes with recombinant IL-37 reduced adipogenesis. The beneficial effects of recombinant IL-37 involved activation of AMPK signaling. In humans, steady-state IL-37 adipose tissue mRNA levels were positively correlated with insulin sensitivity, lower adipose tissue levels of leptin and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes. Gene arrays were performed on epidydimal white adipose tissue samples from wild type and human IL37-overexpressing transgenic mice fed a high fat diet for 16 weeks.
2015-05-18 | E-GEOD-58952 | biostudies-arrayexpress
Project description:Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme regulating cellular energy metabolism across all species. Recent studies have shown the pleiotropic roles of adipose tissue NAD+ biology in adipose tissue and whole-body metabolism. The major purpose of the present study was to test the hypothesis that adipose tissue NAD+ biosynthesis, mediated by nicotinamide phosphoribosyltransferase (NAMPT), is a physiological regulator of whole-body metabolic flexibility. To this end, we analyzed adipocyte-specific Nampt knockout (ANKO) mice and subcutaneous white adipose tissue (WAT) biopsy samples obtained from human subjects. We found ANKO mice preferably utilized glucose substrate during the light period or after prolonged fasting. In contrast, ANKO mice had marked decreases in stimulation of glucose oxidation and suppression of fat oxidation during the postprandial status despite hyperinsulinemia. Data obtained from RNA-sequencing of WAT suggest that loss of NAMPT causes inflammation, oxidative stress, defective fatty acid oxidation, and mitochondrial dysfunction in WAT, key features of obesity and metabolic inflexibility. We also found WAT NAD+ concentration was decreased in people with obesity and insulin resistance compared with those who were non-obese and insulin-sensitive. In addition, bariatric surgery-induced 20% weight loss increased WAT NAD+ concentration in people with obesity. Taken together, our results reveal the importance of adipose tissue NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility. Our results also provide translational and clinical insight into adipose tissue NAD+ biology in obesity and whole-body metabolic health.
2021-07-01 | GSE159397 | GEO
Project description:The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that permanently confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity.
2014-10-31 | GSE57896 | GEO
Project description:Transriptional profiling of white adipose tissue extracted from obese mice. White adipose tissues were extrated from Oma1-deficient mouse and control after 20 weeks of diet-induced obesity. RNA were extracted and hybridated with Mouse Gene 1.0 ST from Affymetrix microarrays.
2012-01-01 | E-GEOD-27525 | biostudies-arrayexpress
Project description:MANUSCRIPT ABSTRACT: The most abundant cellular divalent cations, Mg2+ (mM) and Ca2+ (nM-µM), antagonistically regulate divergent metabolic pathways with several orders of magnitude affinity preference, but its physiological significance of this competition remains largely unknown. In mice consuming a Western diet, genetic ablation of the mitochondrial Mg2+ channel Mrs2 prevents weight gain, enhances mitochondrial activity, decreases fat accumulation in the liver, and causes prominent browning of white adipose. Mrs2 deficiency further restrains citrate efflux from the mitochondria, making it unavailable to support de novo lipogenesis. As citrate is an endogenous Mg2+ chelator, this may represent an adaptive response to a perceived deficit of the cation. Transcriptional profiling of liver and white adipose reveals higher expression of genes involved in glycolysis, b-oxidation, thermogenesis, and HIF-1a-targets, in Mrs2-/- mice that are further enhanced under Western diet-associated metabolic stress. Thus, lowering mMg2+ is sufficient to promote metabolism and dampens diet induced obesity and metabolic syndrome.
2023-05-03 | GSE216538 | GEO
Project description:Different human adipose tissue depots may have functional differences. Subcutaneous human adipose tissue has been extensively studied, but less is known about other depots. Perithyroid (PT) adipose tissue contains not only white adipocytes but also brown adipocytes. The aim of this study was to compare the expression of brown adipocyte containing perithyroid adipose tissue with s.c. adipose tissue.role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders. Expression analysis of paired biopsies from s.c and perithyriod (PT) adipose tissue from nine subjects undergoing surgery in the thyroid region.
2013-01-22 | E-GEOD-27657 | biostudies-arrayexpress
Project description:Two types of adipose tissues, white and brown, are found in mammals. Increasingly novel strategies are being proposed for the treatment of obesity and its associated complications by altering amount and/or activity of BAT using mouse models. We used microarrays to detail the global programme of gene expression in subcutaneous white adipose tissue and brown adipose tissue. White adipose tissue (Subcutaneous region) and brown adipose tissue (intrascapular) were isolated from LACA mice (male, 25 ± 3g ) for RNA extraction and hybridization on Affymetrix microarrays.
2015-04-27 | E-GEOD-67389 | biostudies-arrayexpress