Speaker Abstract

Obesity and Insulin Resistance: Insights from Adipose Cell Biology

David C. W. Lau, Edith Aziz, Gillian Shillabeer and James C. Russell, Dept. of Med. & Loeb Res. Inst., Univ. of Ottawa, Ottawa, ON, K1Y 4E9.

The molecular mechanisms underlying the development of insulin resistance (IR) in obesity were investigated in lean and genetically obese JCR:LA-cp rats, as well as adipose cells cultured from these and Sprague-Dawley rats. Obesity preceded the development of insulin resistance in skeletal muscle in the JCR:LA-cp rat, a model of severe obesity & insulin resistance syndrome. While basal and insulin-mediated glucose uptake in skeletal muscle were unchanged in 4-week old rats, plasma and muscle triacylglycerols (TG) levels were already elevated in the obese compared to those of lean rats. Muscle TG and IR rose progressively with increasing obesity. Treatment with a TG-lowering agent (Medica-16) reversed the plasma and muscle TG abnormalities and IR, suggesting a causal role for obesity and muscle TG in the development of IR. At the cellular level, mature fat cells release a number of paracrine/autocrine mediators that modulate pre-adipocyte growth and insulin-mediated glucose uptake. Adipocyte differentiation factor, some prostaglandins, and low levels of leptin are positive effectors, whereas tumor necrosis factor-a inhibits preadipocyte differentiation and is associated with the development of IR. Hence, obesity contributes to the development of IR and type 2 diabetes through complex multiple pathways. Supported by Can. Diabetes Assoc. & HSFC.