Browse
Submit Data
Databases
API
Help

Dataset Information

34 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Visceral Adipose Tissue Phospholipid Signature of Insulin Sensitivity and Obesity.

ABSTRACT: Alterations in visceral adipose tissue (VAT) are closely linked to cardiometabolic abnormalities. The aim of this work is to define a metabolic signature in VAT of insulin resistance (IR) dependent on, and independent of, obesity. An untargeted UPLC-Q-Exactive metabolomic approach was carried out on the VAT of obese insulin-sensitive (IS) and insulin-resistant subjects (N = 11 and N = 25, respectively) and nonobese IS and IR subjects (N = 25 and N = 10, respectively). The VAT metabolome in obesity was defined among other things by changes in the metabolism of lipids, nucleotides, carbohydrates, and amino acids, whereas when combined with high IR, it affected the metabolism of 18 carbon fatty acyl-containing phospholipid species. A multimetabolite model created by glycerophosphatidylinositol (18:0); glycerophosphatidylethanolamine (18:2); glycerophosphatidylserine (18:0); and glycerophosphatidylcholine (18:0/18:1), (18:2/18:2), and (18:2/18:3) exhibited a highly predictive performance to identify the metabotype of "insulin-sensitive obesity" among obese individuals [area under the curve (AUC) 96.7% (91.9-100)] and within the entire study population [AUC 87.6% (79.0-96.2)]. We demonstrated that IR has a unique and shared metabolic signature dependent on, and independent of, obesity. For it to be used in clinical practice, these findings need to be validated in a more accessible sample, such as blood.

SUBMITTER: Palau-Rodriguez M

PROVIDER: S-EPMC8631729 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

STAT1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity in Obesity.

Project description:Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. 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 a-KO ) enhanced mitochondrial function and accelerated tricarboxylic acid cycle flux coupled with reduced fat cell size in subcutaneous WAT depots. STAT1 a-KO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon-γ activity enhanced insulin sensitivity in diet-induced obesity. Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.

| S-EPMC7679774 | biostudies-literature

Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity.

Project description:There is a rapid global rise in obesity, and the link between obesity and diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which is a member of serine protease inhibitor family. Vaspin cDNA was isolated by from visceral white adipose tissues (WATs) of Otsuka Long-Evans Tokushima fatty (OLETF) rat, an animal model of abdominal obesity with type 2 diabetes. Rat, mouse, and human vaspins are made up of 392, 394, and 395 amino acids, respectively; exhibit approximately 40% homology with alpha1-antitrypsin; and are related to serine protease inhibitor family. Vaspin was barely detectable in rats at 6 wk and was highly expressed in adipocytes of visceral WATs at 30 wk, the age when obesity, body weight, and insulin levels peak in OLETF rats. The tissue expression of vaspin and its serum levels decrease with worsening of diabetes and body weight loss at 50 wk. The expression and serum levels were normalized with the treatment of insulin or insulin-sensitizing agent, pioglitazone, in OLETF rats. Administration of vaspin to obese CRL:CD-1 (ICR) (ICR) mice fed with high-fat high-sucrose chow improved glucose tolerance and insulin sensitivity reflected by normalized serum glucose levels. It also led to the reversal of altered expression of genes relevant to insulin resistance, e.g., leptin, resistin, TNFalpha, glucose transporter-4, and adiponectin. In DNA chip analyses, vaspin treatment resulted in the reversal of expression in approximately 50% of the high-fat high-sucrose-induced genes in WATs. These findings indicate that vaspin exerts an insulin-sensitizing effect targeted toward WATs in states of obesity.

| S-EPMC1180799 | biostudies-literature

STAT1 Dissociates Adipose Tissue Inflammation from Insulin Sensitivity in Obesity

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

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance.

Project description:Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p < 0.001) circulating concentrations of NTN-1 in obesity decreased (p < 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p < 0.01) and insulin levels (p < 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p < 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p < 0.01). NTN1 expression levels were enhanced (p < 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p < 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p < 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.

| S-EPMC9611559 | biostudies-literature

miR-30a Remodels Subcutaneous Adipose Tissue Inflammation to Improve Insulin Sensitivity in Obesity.

Project description:Chronic inflammation accompanies obesity and limits subcutaneous white adipose tissue (WAT) expandability, accelerating the development of insulin resistance and type 2 diabetes mellitus. MicroRNAs (miRNAs) influence expression of many metabolic genes in fat cells, but physiological roles in WAT remain poorly characterized. Here, we report that expression of the miRNA miR-30a in subcutaneous WAT corresponds with insulin sensitivity in obese mice and humans. To examine the hypothesis that restoration of miR-30a expression in WAT improves insulin sensitivity, we injected adenovirus (Adv) expressing miR-30a into the subcutaneous fat pad of diabetic mice. Exogenous miR-30a expression in the subcutaneous WAT depot of obese mice coupled improved insulin sensitivity and increased energy expenditure with decreased ectopic fat deposition in the liver and reduced WAT inflammation. High-throughput proteomic profiling and RNA-Seq suggested that miR-30a targets the transcription factor STAT1 to limit the actions of the proinflammatory cytokine interferon-γ (IFN-γ) that would otherwise restrict WAT expansion and decrease insulin sensitivity. We further demonstrated that miR-30a opposes the actions of IFN-γ, suggesting an important role for miR-30a in defending adipocytes against proinflammatory cytokines that reduce peripheral insulin sensitivity. Together, our data identify a critical molecular signaling axis, elements of which are involved in uncoupling obesity from metabolic dysfunction.

| S-EPMC6245225 | biostudies-literature

Removal of Epididymal Visceral Adipose Tissue Prevents Obesity-Induced Multi-organ Insulin Resistance in Male Mice.

Project description:Obesity is associated with insulin resistance, an important risk factor of type 2 diabetes, atherogenic dyslipidemia, and nonalcoholic fatty liver disease. The major purpose of this study was to test hypothesize that prophylactic removal of epididymal visceral adipose tissue (VAT) prevents obesity-induced multi-organ (liver, skeletal muscle, adipose tissue) insulin resistance. Accordingly, we surgically removed epididymal VAT pads from adult C57BL/6J mice and evaluated in vivo and cellular metabolic pathways involved in glucose and lipid metabolism following chronic high-fat diet (HFD) feeding. We found that VAT removal decreases HFD-induced body weight gain while increasing subcutaneous adipose tissue (SAT) mass. Strikingly, VAT removal prevents obesity-induced insulin resistance and hyperinsulinemia and markedly enhances insulin-stimulated AKT-phosphorylation at serine-473 (Ser473) and threonine-308 (Thr308) sites in SAT, liver, and skeletal muscle. VAT removal leads to decreases in plasma lipid concentrations and hepatic triglyceride (TG) content. In addition, VAT removal increases circulating adiponectin, a key insulin-sensitizing adipokine, whereas it decreases circulating interleukin 6, a pro-inflammatory adipokine. Consistent with these findings, VAT removal increases adenosine monophosphate-activated protein kinase C phosphorylation, a major downstream target of adiponectin signaling. Data obtained from RNA sequencing suggest that VAT removal prevents obesity-induced oxidative stress and inflammation in liver and SAT, respectively. Taken together, these findings highlight the metabolic benefits and possible action mechanisms of prophylactic VAT removal on obesity-induced insulin resistance and hepatosteatosis. Our results also provide important insight into understanding the extraordinary capability of adipose tissue to influence whole-body glucose and lipid metabolism as an active endocrine organ.

| S-EPMC8041347 | biostudies-literature

Obesity, Visceral Adipose Tissue, and Cognitive Function in Childhood.

Project description:ObjectivesTo evaluate the effects of a 9-month physical activity intervention on changes in adiposity and cognitive control based on pretrial weight status (ie, healthy weight vs obese) in children.Study designParticipants included obese (n = 77) and matched healthy-weight (n = 77) preadolescents (8-9 years) who participated in a 9-month physical activity randomized controlled trial. Cognitive function was assessed with an inhibitory control task (modified flanker task).ResultsAfter the 9-month physical activity intervention, participants exhibited a reduction in adiposity. In contrast, children in the waitlist-control condition, particularly children identified as obese pretrial, gained visceral adipose tissue (P= .008). Changes in visceral adipose tissue were related to changes in cognitive performance, such that the degree of reduction in visceral adipose tissue directly related to greater gains in inhibitory control, particularly among obese intervention participants (CI -0.14, -0.04; P= .001).ConclusionsParticipation in a daily physical activity program not only reduces adiposity but also improves children's cognitive function as demonstrated by an inhibitory control task. Furthermore, these findings reveal that the benefits of physical activity to improvements in cognitive function are particularly evident among children who are obese.Trial registrationClinicalTrials.gov: NCT01334359 and NCT01619826.

| S-EPMC5541384 | biostudies-literature

Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue.

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, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue.

| S-EPMC9287736 | biostudies-literature

Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes.

Project description:Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA-mediator of signaling; NPRC-clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity.A cross-sectional study of subjects with a wide range of BMI and glucose tolerance (n?=?50) was conducted, as well as a randomized 12-week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n?=?9) or placebo (n?=?10).NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P???0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P?<?0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P???0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPAR? coactivator-1? and uncoupling protein 1 (P???0.01).Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes.

| S-EPMC5067565 | biostudies-literature

Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals.

Project description:BackgroundIncreased tissue cortisol availability has been implicated in abnormal glucose and fat metabolism in patients with obesity, metabolic syndrome, and type 2 diabetes (T2DM). Our objective was to evaluate whether blockade of glucocorticoid receptor (GR) with mifepristone ameliorates insulin resistance (IR) in overweight/obese subjects with glucose intolerance.MethodsWe conducted a randomized, double-blinded, placebo-controlled, crossover study in overweight/obese individuals (n = 16, 44% female) with prediabetes or mild T2DM but not clinical hypercortisolism. Mifepristone (50 mg every 6 h) or placebo was administered for 9 days, followed by crossover to the other treatment arm after a washout period of 6 to 8weeks. At baseline and following each treatment, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT) were performed. Insulin sensitivity was measured using FSIVGTT [primary outcome: insulin sensitivity index (SI)] and OGTT [Matsuda index (MI) and oral glucose insulin sensitivity index (OGIS)]. Hepatic and adipose insulin resistance were assessed using hepatic insulin resistance index (HIRI), and adipose tissue insulin sensitivity index (Adipo-SI) and adipo-IR, derived from the FSIVGTT.ResultsMifepristone administration did not alter whole-body glucose disposal indices of insulin sensitivity (SI, MI, and OGIS). GR blockade significantly improved Adipo-SI (61.7 ± 32.9 vs 42.8 ± 23.9; P = 0.002) and reduced adipo-IR (49.9 ± 45.9 vs 65.5 ± 43.8; P = 0.004), and HIRI (50.2 ± 38.7 vs 70.0 ± 44.3; P = 0.08). Mifepristone increased insulin clearance but did not affect insulin secretion or β-cell glucose sensitivity.ConclusionShort-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism.

| S-EPMC8063260 | biostudies-literature

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