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.