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Am J Physiol Endocrinol Metab (September 27, 2005). doi:10.1152/ajpendo.00293.2005
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Submitted on June 29, 2005
Accepted on September 23, 2005

Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats

Colleen M Novak1*, Catherine M Kotz2, and James A Levine3

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

* To whom correspondence should be addressed. E-mail: novak.colleen{at}mayo.edu.

Non-exercise 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 rat (DR) strain, to investigate how access to a high-fat diet alters SPA and the associated energy expenditure (i.e., NEAT). Diet-induced obese 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 if 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 hours. Using the response to vehicle as a baseline, the DR rats showed significantly greater increase in NEAT compared to 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.




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