Ontogeny of diet-induced obesity in selectively bred Sprague-Dawley rats

1 Research Diets, Inc., New Brunswick 08901; 2 Neurology Service (127C) Veterans Affairs Medical Center, East Orange 07018; and 3 Department 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 Address for reprint requests and other correspondence: B. E. Levin, Neurology Service (127C), VA Medical Center, 385 Tremont Ave., E. Orange, NJ 07018-1095 (E-mail: levin{at}umdnj.edu ).