Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alcohol dehydrogenase 1B is crucial for adipocyte homeostasis

ABSTRACT: Background. Alcohol dehydrogenase (ADH1B), encoded by the ADH1B gene, is a cytosolic enzyme mainly known for its role in ethanol catabolism in the liver. A few studies have paved the way to show an equally important role of ADH1B in adipocytes. This study aimed to better identify the cellular mechanisms and signaling pathways involving ADH1B in adipose tissue and to determine if ADH1B variants might contribute to adipose tissue dysfunction. Results. We showed that CRISPR-Cas9-mediated ADH1B knockout (KO) in human adipose stem cells (ASC) abolished adipocyte differentiation and decreased insulin response. This was accompanied by oxidative stress, altered mitochondrial functions, and cellular senescence. Lipidomic analysis revealed that ADH1B deficiency results in a major remodeling of lipid composition in ASC. An ADH1B homozygous loss-of-function variant was also identified in a patient presenting with a lipodystrophic and insulin resistant syndrome associated with major liver dysfunction, leading to early death. Discussion. This translational study underlines the crucial role of ADH1B in adipose tissue. It unveils cellular mechanisms accounting for its key role in adipogenesis, and adipocyte homeostasis. This study also identifies ADH1B as a candidate gene in monogenic forms of lipodystrophic and insulin resistant syndromes.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Cultured Cells

SUBMITTER: Jérémie Gautheron

PROVIDER: ST002400 | MetabolomicsWorkbench | Tue Dec 13 00:00:00 GMT 2022

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Similar Datasets

System level analysis of insulin action revels insight into whole body metabolism and insulin action in muscle and adipose tissue

Project description:Muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environment interactions and was strongly correlated with hyperinsulinemia and decreased levels of ten key glycolytic enzymes. Remarkably, there was no relationship between muscle and adipose tissue insulin resistance. Adipocyte size profoundly varied across strains and diets, and this was strongly correlated with adipose tissue insulin action. The A/J strain in particular exhibited marked adipocyte insulin resistance and hypertrophy despite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophy per se in systemic insulin resistance. These data demonstrate that muscle and adipose tissue insulin resistance can occur independently and underscore the need for tissue-specific interrogation to understand metabolic disease.

2022-02-24 | PXD029680 | Pride

CD1d-restricted NKT cell function prevents insulin resistance in lean mice, and is regulated by adipocytes and is regulated by adipocytes

Project description:Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell–deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue–resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue–resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance. four samples

2012-08-06 | E-GEOD-39534 | biostudies-arrayexpress

CD1d-restricted NKT cell function prevents insulin resistance in lean mice, and is regulated by adipocytes and is regulated by adipocytes

2012-08-07 | GSE39534 | GEO

MBOAT7-Driven Lysophosphatidylinositol Acylation in Adipocytes Contributes to Systemic Glucose Homeostasis

Project description:We previously demonstrated that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7, the gene encoding Membrane Bound O-Acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. We generated floxed Mboat7 mice and created hepatocyte- and adipocyte-specific knockout mice using Cre-recombinase mice under the control of the albumin and adiponectin promoter, respectively. After chow and high fat diet feeding (60% kCal fat), mice were subjected to metabolic phenotyping and tissues to molecular workup and analysis. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ~100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, we found that adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.

2023-05-10 | PXD039894 | Pride

Control of cholesterol-induced adipocyte inflammation by the Nfe2l1-Atf3 pathway

Project description:While adipocytes are critical pillars of energy metabolism, their dysfunction is linked to adipose tissue (AT) inflammation, insulin resistance, and ectopic lipotoxicity in cardiometabolic diseases. However, he mechanisms causing adipocyte inflammation and insulin resistance remain unclear. Here, we show that excess cholesterol induces adipocyte dysfunction, which is suppressed by the transcription factor Nfe2l1 (nuclear factor erythroid derived-2, like-1). Nfe2l1 is required to sustain proteasome function in adipocytes and proteotoxic stress induces adipocyte inflammation via the activation of Atf3. In humans, the Nfe2l1-proteasome pathway is inversely correlated to body mass index (BMI) in an adipose-depot specific manner. In mice, loss of adipocyte Nfe2l1 caused AT inflammation with a pronounced infiltration of macrophages and T cells. Mice lacking adipocyte Nfe2l1 displayed severe adipocyte dysfunction during diet-induced obesity (DIO), characterized by lower adipokine levels, steatosis, glucose intolerance and insulin resistance. Nfe2l1ΔAT mice on an Apoe-deficient (Apoe-/-) background fed a cholesterol-rich Western Diet (WD), developed a lipoatrophy-like syndrome, dyslipidemia, and enhanced atherosclerosis. Our results reveal an important role for proteasome-mediated proteostasis in adipocytes and indicate that Nfe2l1 is linked to metabolic health in humans and preclinical mouse models. Promoting proteostasis in adipocytes may thus alleviate inflammation in obesity, potentially averting adverse cardiometabolic outcomes.

2024-07-30 | GSE273101 | GEO

Inhibiting phosphatidylcholine remodeling in adipose tissue increases insulin sensitivity [RNA-Seq]

Project description:Cell membrane phosphatidylcholine composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane phosphatidylcholine saturation are implicated in metabolic disorders. Here, we identified LPCAT3 as the major isoform of LPCAT in adipose tissues and created adipocyte-specific Lpcat3-knockout mice to study adipose tissue lipid metabolism. Transcriptome sequencing and plasma adipokine profiling were used to investigate how LPCAT3 regulates adipose tissue insulin signaling. LPCAT3 deficiency reduced polyunsaturated phosphatidylcholines in adipocyte plasma membranes, increasing insulin sensitivity. LPCAT3 deficiency influenced membrane lipid rafts, which activated insulin receptors and AKT in adipose tissue, and attenuated diet-induced insulin resistance. Conversely, higher LPCAT3 activity in adipose tissues from ob/ob, db/db, and high-fat diet-fed mice reduced insulin signaling. Adding polyunsaturated phosphatidylcholines to mature human or mouse adipocytes in vitro worsened insulin signaling. We suggest that targeting LPCAT3 in adipose tissues to manipulate membrane phospholipid saturation is a new strategy to treat insulin resistance.

2024-07-16 | GSE235302 | GEO

Inhibiting phosphatidylcholine remodeling in adipose tissue increases insulin sensitivity [scRNA-Seq]

2024-07-16 | GSE234884 | GEO

Linc-ADAIN, A Human Adipose LincRNA Regulates Adipogenesis by Modulating KLF5 and IL-8 mRNA stability

Project description:Adipose tissue remodeling and dysfunction, characterized by increased inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2DM) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here we describe the functions of linc-ADAIN (ADipose Anti-INflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and IL-8 mRNA stability and translation, by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, led to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo, KD of linc-ADAIN in human ASC hTERT adipocytes implanted into mice, increased adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. Linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage.

2024-04-16 | GSE263852 | GEO

Gene expression analysis of subcutaneous and omental adipose tissue from obese, insulin-resistant women

Project description:The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. Subcutaneous and omental adipose tissue and serum were obtained from 29 obese nondiabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed. In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.

2015-12-07 | GSE73108 | GEO

Human adipose insulin resistance

Project description:Adipocytes play a major role in whole body fuel homeostasis. Integrated proteomic analysis of adipose from insulin resistant versus healthy humans or mice or in 3T3-L1 adipocytes revealed defects in the mevalonate/coenzyme Q (CoQ) biosynthesis pathway as a unifying feature of adipocyte insulin resistance. CoQ was decreased selectively in mitochondria in all insulin resistant conditions and this was associated with a selective increase in mitochondrial oxidative stress. CoQ supplementation lowered mitochondrial oxidative stress and reversed insulin resistance in vitro and in vivo. Decreasing mitochondrial CoQ by genetic or pharmacological means caused insulin resistance by increasing mitochondrial oxidants from complex II. Our data suggest that loss of mitochondrial CoQ is a proximal driver of mitochondrial oxidative stress and insulin resistance. These findings may explain why statin use is associated with insulin resistance, and suggest that mitochondrial CoQ may be an effective therapeutic target for treating insulin resistance in humans.

2018-02-09 | PXD006891 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data