Insulin Resistance in SHR/NDmc-cp Rats Correlates with Enlarged Perivascular Adipocytes and Endothelial Cell Dysfunction in Skeletal Muscle

Abstract

Ectopic adipose tissue in skeletal muscle is implicated in the development of insulin resistance, which is frequently induced by abnormal dietary habits such as excessive eating and a high-fat diet. However, the characteristics of ectopic adipocytes are unknown. In this study, we investigated the characteristics of ectopic adipocytes in the skeletal muscle of spontaneously hypertensive corpulent congenic (SHR/NDmc-cp) rats as a model of insulin resistance from excessive eating. SHR/NDmc-cp rats displayed overt insulin resistance with high plasma glucose, insulin, and triacylglycerol concentrations relative to control Wistar-Kyoto (WKY) rats. In contrast, streptozotocin (STZ)-treated WKY rats had high glucose but low insulin concentrations. Ectopic adipocytes were found around blood vessels in the gastrocnemius in SHR/NDmc-cp rats. Areas of perivascular adipocytes and protein expression of resistin were greater in SHR/NDmc-cp rats than in control and STZ-treated WKY rats. The level of the phosphorylated (active) form of endothelial nitric oxide synthase in the gastrocnemius was lower in SHR/NDmc-cp rats than in the other groups. Insulin-resistant SHR/NDmc-cp rats showed enlarged perivascular adipocytes and greater endothelial cell dysfunction in the gastrocnemius.