Abdominal obesity, fatty acids and insulin resistance

Abstract

We have been interested in the links among obesity, insulin resistance and Type 2 diabetes. We have investigated this link in the canine, allowing us to do longitudinal studies, to measure molecules in specific body compartments, and to control and monitor body weight and activity. Fat feeding for 22 weeks induces insulin resistance, despite a small increase in body weight (~10%), due to enhancement of visceral and subcutaneous adipose. Adipocytes in lean animals are defined by a single size distribution. Increased fat in the visceral fat depot develops four classes of adipocytes of varying size. The larger fat cells are correlated with whole-animal insulin resistance. No similar population is observed in subcutaneous cells confirming the importance of the visceral fat depot per se in the development of insulin resistance. Importance is confirmed by a significant increase in insulin sensitivity with omentectomy in the dog. The sympathetic nervous system plays a role as free fatty acids (FFA) are released from the visceral fat depot in pulsatile fashion. Nocturnal FFA lead to liver insulin resistance and fatty liver. The latter reduces insulin clearance by the liver, resulting in hyperinsulinemia and peripheral insulin resistance. These events result in the so-called insulin resistance or “metabolic” syndrome.