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

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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:AbatractObesity is known to be associated with adipose tissue inflammation and insulin resistance. Importantly, in obesity, the accumulation of proinflammatory macrophages in adipose tissue correlates with insulin resistance. We hypothesized that the receptor for advanced glycation end products (RAGE) and associated ligands are involved in adipose tissue insulin resistance, and that the activation of the AGE-RAGE axis plays an important role in obesity-associated inflammation. C57BL/6J mice (WT) and RAGE deficient (RAGE-/-) mice were fed a high fat diet (HFD) and subjected to glucose and insulin tolerance tests. Epdidymal adipose tissue (eAT) was collected and adipose stromal vascular cells isolated using flow cytometry. Visceral adipose tissue macrophage polarization was assessed by quantitative real time PCR. Immunoblotting was performed to evaluate the insulin signaling in adipose tissues. In additional studies, cell trafficking was assessed by injecting labeled blood monocytes into recipient mice. RAGE-/- mice displayed improved insulin sensitivity and glucose tolerance, accompanied by decreased body weight and eAT mass. Exogenous methylglyoxal (MGO) impaired insulin-stimulated AKT signaling in adipose tissues from WT mice fed a normal chow diet, but not in RAGE-/- mice. In contrast, in obese mice, treatment with MGO did not reduce insulin-induced phosphorylation of AKT in WT-HFD mice. Moreover, insulin-induced AKT phosphorylation was found to be impaired in adipose tissue from RAGE-/--HFD mice. RAGE-/- mice displayed improved inflammatory profiles and evidence for increased adipose tissue browning. This observation is consistent with the finding of reduced plasma levels of FFA, glycerol, IL-6, and leptin in RAGE-/- mice compared to WT mice. Collectively the data demonstrate that RAGE-mediated adipose tissue inflammation and insulin-signaling are potentially important mechanisms that contribute to the development of obesity-associated insulin resistance.

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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