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APPETITE, OBESITY AND METABOLISM
1Research Diets, Inc., New Brunswick 08901; 2Neurology Service (127C) Veterans Affairs Medical Center, East Orange 07018; and 3Department of Neurosciences, New Jersey Medical School, Newark, New Jersey 07103
Submitted 30 April 2003 ; accepted in final form 23 May 2003
Outbred Sprague-Dawley rats selectively bred for their propensity to
develop diet-induced obesity (DIO) become heavier on low-fat diet than those
bred to be diet resistant (DR) beginning at 
5 wk of age. Here we assessed
the development of metabolic and neural functions for insights into the
origins of their greater weight gain. From week 5 to week 10,
chow-fed DIO rats gained 15% more body weight and ate 14% more calories
but had only slightly greater adiposity and plasma leptin than DR rats. From
day 3 through week 10, DIO and DR rats had similar mRNA
expression of arcuate nucleus neuropeptide Y, proopiomelanocortin,
agouti-related peptide, and all splice variants of the leptin receptor (OB-R).
When fed a high-energy (HE; 31% fat) diet, 7-wk-old DIO rats had a 240%
increase in plasma leptin levels after only 3 days. Despite this early leptin
rise, they maintained a persistent hyperphagia and became more obese than
chow-fed DIO rats and DR rats fed chow or HE diet. Their failure to reduce
caloric intake, despite high levels of leptin, suggests that selectively bred
DIO rats might have reduced leptin sensitivity similar to that seen in the
outbred DIO parent strain.
leptin receptor; neuropeptide Y; proopiomelanocortin; agouti-related peptide; arcuate nucleus
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