Effects of multiple cycles of weight loss and regain on the body weight regulatory system in rats.

We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. Thirty-six male Wistar rats were divided into three weight-matched groups: weight cyclers (n = 18), ad libitum-fed controls (n = 9), and maturity controls (n = 9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding. Controls ate ad libitum. Maturity controls ate ad libitum and then weight cycled the final two rounds to evaluate the effect of age in later cycles. Cyclers' postdiet plateau weight became progressively lower than that of controls. With each weight loss, ghrelin increased, while insulin and leptin decreased; the magnitude of these changes did not differ across cycles. After four rounds, cyclers' weight (504 ± 7 vs. 540 ± 22 g; P < 0.05) and percent body fat (11.7 vs. 15.2%; P < 0.05) were lower than in controls. After a 4-mo follow-up period of ad libitum feeding, cyclers maintained a lower total fat-pad mass versus controls (8.6 ± 0.5 vs. 15.9 ± 3.6 g; P < 0.01) and a lower glucose area-under-the-curve on oral glucose tolerance tests (P < 0.05). Repeated weight-loss cycles exerted positive effects, durably lowering defended levels of body adiposity and improving glucose tolerance.