DEFENSE OF DIFFERING BODY-WEIGHT SET POINTS IN DIET-INDUCED OBESE ANDRESISTANT RATS

Among outbred Sprague-Dawley rats, approximately one-half develop diet -induced obesity (DIO) and one-half are diet resistant (DR) on a diet relatively high in fat and energy content (HE diet). Here we examined the defense of body weight in these two phenotypes. After HE diet for 13 wk, followed by chow for 6 wk, DR rats gained weight comparably but their plasma leptin levels fell to 54% of chow-fed controls. When a p alatable liquid diet (Ensure) was added for 13 wk, other DR rats becam e obese. But when switched to chow, their intakes fell by 60%, and bod y add retroperitoneal (RP) fat pad weighs and plasma leptin and insuli n levels all declined for 2 wk and then stabilized at control levels a fter 6 wk. In contrast, comparably obese DIO rats decreased their inta ke by only 20%, and their weights plateaued when they were switched to chow after 13 wk on HE diet. When a subgroup of these DIO rats was re stricted to 60% of prior intake, their weights fell to chow-fed contro l levels over 2 wk. But, their leptin and insulin levels both fell dis proportionately to 30% of controls. When no longer restricted, their i ntake and feed efficiency rose immediately, and their body and RP pad weights and leptin and insulin levels rose to those of unrestricted DI O rats within 2 wk. Thus diet and genetic background interact to estab lish high (DIO) or low (DR) body weight set points, which are then def ended against subsequent changes in diet composition and/or energy ava ilability. If leptin affects energy homeostasis, it does so differenti ally in DIO vs. DR rats since comparably low and high levels were asso ciated with differing patterns of weight change between the two phenot ypes.