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Am J Physiol Endocrinol Metab 290: E396-E403, 2006. First published September 27, 2005; doi:10.1152/ajpendo.00293.2005
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Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats

Colleen M. Novak,1 Catherine M. Kotz,2,3,4 and James A. Levine1,3

1Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester; 2Veterans Affairs Medical Center; 3Minnesota Obesity Center, Minneapolis; and 4Departments of Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota

Submitted 29 June 2005 ; accepted in final form 23 September 2005

Nonexercise activity thermogenesis (NEAT), the most variable component of energy expenditure, can account for differential capacities for human weight gain. Also highly variable, spontaneous physical activity (SPA) may similarly affect weight balance in animals. In the following study, we utilized the rat model of obesity, the diet-induced obese (DIO) rat, as well as the diet-resistant (DR) rat strain, to investigate how access to a high-fat diet alters SPA and the associated energy expenditure (i.e., NEAT). DIO and DR rats showed no differences in the amount of SPA before access to the high-fat diet. After 29 days on a high-fat diet, the DIO rats showed significant decreases in SPA, whereas the DR rats did not. Next, we wanted to determine whether the DIO and DR rats showed differential sensitivity to microinjections of orexin into the paraventricular nucleus of the hypothalamus (PVN). Unilateral guide cannulae were implanted, aimed at the PVN. Orexin A (0, 0.125, 0.25, and 1.0 nmol in 500 nl) was microinjected through the guide cannula into the PVN, then SPA and energy expenditure were measured for 2 h. Using the response to vehicle as a baseline, the DR rats showed significantly greater increase in NEAT compared with the DIO rats. These data indicate that diet-induced obesity is associated with decreases in SPA and a lack of increase in NEAT. A putative mechanism for changes in NEAT that accompany obesity is a decreased sensitivity to the NEAT-activating effects of neuropeptides such as orexin.

nonexercise activity thermogenesis; paraventricular nucleus of the hypothalamus; high-fat diet; hypocretin


Address for reprint requests and other correspondence: J. A. Levine, Endocrine Research Unit, Joseph 5-194, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905 (e-mail: levine.james{at}mayo.edu)




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