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1 Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota, United States
2 Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota, United States; Medicine, University of Minnesota, Minneapolis, Minnesota, United States; Psychology, University of Minnesota, Minneapolis, Minnesota, United States; Psychiatry, University of Minnesota, Minneapolis, Minnesota, United States; Minnesota Obesity Center, Minneapolis, Minnesota, United States; VA Medical Center, Minneapolis, Minnesota, United States
3 VA Medical Center, Minneapolis, Minnesota, United States
4 Endocrine Research Unit, Mayo Clinic Rochester, Rochester, Minnesota, United States; Minnesota Obesity Center, Minneapolis, Minnesota, United States
5 Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota, United States; Minnesota Obesity Center, Minneapolis, Minnesota, United States; VA Medical Center, Minneapolis, Minnesota, United States
* To whom correspondence should be addressed. E-mail: kotzx004{at}umn.edu.
Selectively-bred obesity resistant (DR, diet resistant) rats weigh less than obesity prone (DIO, diet-induced obese) rats despite comparable daily caloric intake, suggesting phenotypic energy expenditure differences. Human data suggest that obesity is maintained by reduced ambulatory or spontaneous physical activity (SPA). The neuropeptide orexin A robustly stimulates SPA. We hypothesized that DR rats have greater: 1) basal SPA, 2) orexin A-induced SPA and 3) preproorexin, OX1R and OX2R mRNA, compared to DIO rats. A group of age-matched out-bred Sprague-Dawley rats were used as additional controls for the behavioral studies. DIO, DR and Sprague-Dawley rats with dorsal-rostral lateral hypothalamic (rLHa) cannulae were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 µl). SPA and food intake were measured for 2 h after injection. Preproorexin and orexin 1 and 2 receptor (OX1R and OX2R) mRNA in the rLHa and whole hypothalamus were measured by real-time RT-PCR. Orexin A significantly stimulated feeding in all rats. Orexin A-induced SPA was significantly greater in DR and Sprague-Dawley rats than in DIO rats. Two month old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-month old DR rats had elevated OX1R and OX2R mRNA compared to DIO rats, although this increase was significant for OX2R only at this age. Thus, DR rats show elevated basal and orexin A-induced SPA associated with increased OX1R and OX2R gene expression, suggesting that differences in orexin A signaling through OX1R and OX2R may mediate DIO and DR phenotypes.
This article has been cited by other articles:
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  C. M. Kotz, J. A. Teske, and C. J. Billington Neuroregulation of nonexercise activity thermogenesis and obesity resistance Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R699 - R710. [Abstract] [Full Text] [PDF]
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B. E. Levin Orexins: neuropeptides for all seasons and functions Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R885 - R888. [Full Text] [PDF]
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