Be. Levin et Re. Keesey, DEFENSE OF DIFFERING BODY-WEIGHT SET POINTS IN DIET-INDUCED OBESE ANDRESISTANT RATS, American journal of physiology. Regulatory, integrative and comparative physiology, 43(2), 1998, pp. 412-419
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.