REDUCED INSULIN SUPPRESSION OF GLUCOSE APPEARANCE IS RELATED TO SUSCEPTIBILITY TO DIETARY OBESITY IN RATS

To examine the relationship between insulin action and body weight reg ulation in male rats, the following studies were performed. In study 1 , rats (n = 31) were fed a low-fat diet (LFD) for 4 wk, and then gluco se kinetics were estimated under basal and hyperinsulinemic conditions using the glucose clamp. After clamps, these same rats were placed on a high-fat diet (HFD) for 5 wk. In study 2, rats (n = 30) were fed an LFD for 3 wk and then a high-sucrose diet for 1 wk to produce selecti ve hepatic insulin resistance. Clamps were then performed, and after c lamps, these same rats were placed on an HFD for 5 wk. In study 3, rat s (n = 30) were fed an LFD for 1 wk and then a high-sucrose diet for 3 wk to produce widespread insulin resistance. Clamps were then perform ed, and after clamps, these same rats were placed on an HFD for 5 wk. The rate of glucose appearance (R(a)) during the hyperinsulinemic clam ps was the only pre-HFD variable that correlated (r = 0.49, P < 0.01 i n study 1; r = 0.51, P < 0.001 in study 2) with weight gain on the HFD . Clamp R, also correlated with energy intake on the HFD in study 1 (r = 0.64, P < 0.001) and study 2 (r = 0.59, P < 0.001). Clamp R, and en ergy intake on the HFD accounted for similar portions of the variance in body weight gain on the HFD. Weight gain and fat-pad mass were incr eased (P < 0.05) in study 2 compared with study 1. In study 3, pre-HFD glucose kinetics were not correlated with energy intake or weight gai n on the HFD. Widespread insulin resistance did not significantly redu ce the rate of weight gain on the HFD. Thus insulin action on R, can i nfluence body weight gain on an HFD. The effects of R, on body weight gain appear to be mediated via effects on energy intake. Selective hep atic insulin resistance can increase body weight gain on an HFD, but w idespread insulin resistance does not significantly reduce HFD-induced weight gain.