Effect of Long-Term Somatotropin Treatment on Body Composition and Life Span in Aging Obese Zucker Rats

Abstract

The objective of this work was to test the hypothesis that a somatotropin (STH)-induced reduction in body fat would prolong the life span of the obese Zucker rat. Two experiments were conducted. In the first experiment, male and female, lean and obese Zucker rats were treated with STH (0 or 2 mg/d bovine STH) for 4 weeks, beginning at 7 months of age. Across phenotypes, STH treatment increased the growth rate by 159%, muscle weights by 14%, and circulating insulin-like growth factor (IGF)-1 by 23%, and decreased carcass fat by 21% (P < 0.05). The second experiment was a longevity trial to determine whether these changes in body composition would increase the life span of the obese rat. Beginning at 7 months of age, individually housed, male and female, lean and obese rats were assigned to daily STH treatments (0 or 2 mg/d). Rats were monitored daily, and sick or moribund rats were euthanized and necropsied to determine existing pathologies. The average life span of the lean rats was 661 days and was unaffected by STH treatment (639 days, NS) or gender. Average life span of the vehicle-injected obese rats (435 days) was less than that of the lean group (P < 0.001). STH treatment of the obese rats resulted in a further reduction of life span (349 days, P < 0.02). The predominant pathology observed across the treatment groups was renal disease, characterized by progressive glomerulonephropathy. Thus, although exogenous STH was able to reduce carcass lipid and to increase lean tissue mass in obese rats, there was no improvement in longevity. In contrast to the hypothesis, STH actually reduced the life span of the obese rat. It is likely that STH treatment accelerated the development of progressive glomerulonephropathy in the obese rat.