Teske J A, Levine A S, Kuskowski M, Levine J A, Kotz C M
Department of Food Science and Nutrition, University of Minnesota, Saint Paul, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R889-99. doi: 10.1152/ajpregu.00536.2005. Epub 2006 Jun 8.
Selectively-bred obesity-resistant [diet resistant (DR)] rats weigh less than obesity-prone [diet-induced obese (DIO)] 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, orexin 1 and 2 receptor (OX1R and OX2R) mRNA, compared with 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) cannulas were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 microl). SPA and food intake were measured for 2 h after injection. Preproorexin, 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-mo-old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-mo-old DR rats had elevated OX1R and OX2R mRNA compared with 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.
选择性培育的抗肥胖[饮食抗性（DR）]大鼠尽管每日热量摄入相当，但体重却比易肥胖[饮食诱导肥胖（DIO）]大鼠轻，这表明存在表型能量消耗差异。人类数据表明，肥胖是由非自主性或自发性身体活动（SPA）减少所维持的。神经肽食欲素A能有力地刺激SPA。我们假设，与DIO大鼠相比，DR大鼠具有更高的：1）基础SPA；2）食欲素A诱导的SPA；3）前食欲素原、食欲素1和2受体（OX1R和OX2R）mRNA。一组年龄匹配的远交系Sprague-Dawley大鼠用作行为学研究的额外对照。对具有背侧-嘴侧下丘脑外侧（rLHa）插管的DIO、DR和Sprague-Dawley大鼠注射食欲素A（0、31.25、62.5、125、250和500 pmol/0.5微升）。注射后2小时测量SPA和食物摄入量。通过实时RT-PCR测量rLHa和整个下丘脑中的前食欲素原、OX1R和OX2R mRNA。食欲素A显著刺激所有大鼠的进食。食欲素A诱导的SPA在DR和Sprague-Dawley大鼠中显著高于DIO大鼠。2月龄的DR大鼠rLHa中的OX1R和OX2R mRNA显著高于DIO大鼠，但前食欲素原水平相当。8月龄的DR大鼠与DIO大鼠相比，OX1R和OX2R mRNA升高，尽管仅在这个年龄OX2R的增加具有显著性。因此，DR大鼠表现出基础和食欲素A诱导的SPA升高，这与OX1R和OX2R基因表达增加相关，表明通过OX1R和OX2R的食欲素A信号差异可能介导DIO和DR表型。
