Dataset Information

Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance.

ABSTRACT:

Context

Insulin resistance is associated with inflammation, fibrosis, and hypoxia in adipose tissue.

Objective

This study was intended to better characterize the extracellular matrix (ECM) and vascularity of insulin-resistant adipose tissue.

Design

Adipose expression of collagens, elastin, and angiogenic factors was assessed using real-time RT-PCR and immunohistochemistry (IHC) in abdominal sc adipose tissue. Adipocyte-macrophage coculture experiments examined the effects of polarized macrophages on adipose ECM gene expression, and the effects of collagens were measured in an angiogenesis assay.

Participants and setting

A total of 74 nondiabetic subjects participated at a University Clinical Research Center.

Interventions

Interventions included baseline adipose biopsy and measurement of insulin sensitivity.

Main outcome measures

Outcome measures included characterization of vascularity and ECM in adipose tissue.

Results

CD31 (an endothelial marker) mRNA showed no significant correlation with body mass index or insulin sensitivity. In a subgroup of 17 subjects (nine obese, eight lean), CD31-positive capillary number in obese was decreased by 58%, whereas larger vessels were increased by 70%, accounting for the lack of change in CD31 expression with obesity. Using IHC, obese (compared with lean) subjects had decreased elastin and increased collagen V expression, and adipocytes cocultured with M2 macrophages had reduced elastin and increased collagen V expression. In obese subjects, collagen V was colocalized with large blood vessels, and the addition of collagen V to an angiogenesis assay inhibited endothelial budding.

Conclusions

The adipose tissue from obese/insulin-resistant subjects has fewer capillaries and more large vessels as compared with lean subjects. The ECM of adipose tissue may play an important role in regulating the expandability as well as angiogenesis of adipose tissue.

SUBMITTER: Spencer M

PROVIDER: S-EPMC3232606 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance.

Spencer Michael M Unal Resat R Zhu Beibei B Rasouli Neda N McGehee Robert E RE Peterson Charlotte A CA Kern Philip A PA

The Journal of clinical endocrinology and metabolism 20111012 12

<h4>Context</h4>Insulin resistance is associated with inflammation, fibrosis, and hypoxia in adipose tissue.<h4>Objective</h4>This study was intended to better characterize the extracellular matrix (ECM) and vascularity of insulin-resistant adipose tissue.<h4>Design</h4>Adipose expression of collagens, elastin, and angiogenic factors was assessed using real-time RT-PCR and immunohistochemistry (IHC) in abdominal sc adipose tissue. Adipocyte-macrophage coculture experiments examined the effects o ...[more]

PMID: 21994960

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Project description:BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy obese (MHO; n = 15), and metabolically unhealthy obese (MUO; n = 20).RESULTSAT pO2 progressively declined from the MHL to the MHO to the MUO group, and was positively associated with hepatic and whole-body insulin sensitivity. AT pO2 was positively associated with the expression of genes involved in BCAA catabolism, in conjunction with an inverse relationship between AT pO2 and plasma BCAA concentrations. AT pO2 was negatively associated with AT gene expression of markers of inflammation and fibrosis. Plasma PAI-1 increased from the MHL to the MHO to the MUO group and was negatively correlated with AT pO2, whereas the plasma concentrations of other cytokines and chemokines were not different among the MHL and MUO groups.CONCLUSIONThese results support the notion that reduced AT oxygenation in individuals with obesity contributes to insulin resistance by increasing plasma PAI-1 concentrations and decreasing AT BCAA catabolism and thereby increasing plasma BCAA concentrations.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants K01DK109119, T32HL130357, K01DK116917, R01ES027595, P42ES010337, DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK052574 (Digestive Disease Research Center), and UL1TR002345 (Clinical and Translational Science Award); NIH Shared Instrumentation Grants S10RR0227552, S10OD020025, and S10OD026929; and the Foundation for Barnes-Jewish Hospital.

Dataset Information

Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance.

Context

Objective

Design

Participants and setting

Interventions

Main outcome measures

Results

Conclusions

Publications

Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance.

Similar Datasets

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