title: The act of voluntary wheel running reverses dietary hyperphagia and increases leptin signaling in ventral tegmental area of aged obese rats.
abstract: To test the hypothesis that exercise increases central leptin signaling, and thus reduces dietary weight gain in an aged obese model, we assessed the effects of voluntary wheel running (WR) in 23-month-old F344×BN rats fed a 60% high-fat (HF) diet for 3 months. After 2 months on the HF diet, half of the rats were provided access to running wheels for 2 weeks while the other half remained sedentary. Following the removal of the wheels, physical performance was evaluated, and 4 weeks later leptin signaling was assessed in hypothalamus and VTA after an acute bout of WR. Introduction of a HF diet led to prolonged hyperphagia (63.9 ± 7.8 kcal/day on chow diet vs. 88.1 ± 8.2 kcal/day on high-fat diet (when food intake stabilized), p < 0.001). As little as 9 (ranging to 135) wheel revolutions per day significantly reduced caloric consumption of HF food (46.8 ± 11.2 kcal/day) to a level below that on chow diet (63.9 ± 7.8 kcal/day, p < 0.001). After 2 weeks of WR, body weight was significantly reduced (7.9 ± 2.1% compared with prerunning weight, p < 0.001), and physical performance (latency to fall from an incline plane) was significantly improved (p = 0.04). WR significantly increased both basal (p = 0.04) and leptin-stimulated (p = 0.001) STAT3 phosphorylation in the ventral tegmental area (VTA), but not in the hypothalamus. Thus, in aged dietary obese rats, the act but not the extent of voluntary WR is highly effective in reversing HF consumption, decreasing body weight, and improving physical performance. It appears to trigger a response that substitutes for the reward of highly palatable food that may be mediated by increased leptin signaling in the VTA.
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA. sasha1@ufl.edu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Shapiro
authors.forename: Kit-Yan
authors.initials: KY
authors.lastname: Cheng
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Gao
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Seo
authors.forename: Steve
authors.initials: S
authors.lastname: Anton
authors.forename: Christy S
authors.initials: CS
authors.lastname: Carter
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nihal
authors.initials: N
authors.lastname: Tumer
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Scarpace
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001835:Body Weight; D004041:Dietary Fats; D004195:Disease Models, Animal; D005247:Feeding Behavior; D006963:Hyperphagia / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control*; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D010805:Physical Conditioning, Animal / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D020738:Leptin