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1 Research Diets, Inc., New Brunswick, NJ, USA
2 Neurology Service (127C), Veterans Affairs Medical Center, East Orange, NJ, USA; Department of Neurosciences, New Jersey Medical School, Newark, NJ, USA
* To whom correspondence should be addressed. E-mail: levin{at}umdnj.edu.
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 ~5wk of age. Here we assessed the development of metabolic and neural functions for insights into the origins of their greater weight gain. From weeks 5-10, 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, 7wk old DIO rats had a 240% increase in plasma leptin levels after only 3d. 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 suggest that selectively bred DIO rats might have reduced leptin sensitivity similar to that seen in the outbred DIO parent strain.
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