title: High and low activity rats: elevated intrinsic physical activity drives resistance to diet-induced obesity in non-bred rats.
abstract: OBJECTIVE
  Humans and rodents show large variability in their individual sensitivity to diet-induced obesity (DIO), which has been associated with differences in intrinsic spontaneous physical activity (SPA). Evidence from genetic and out-bred rat obesity models shows that higher activity of the orexin peptides results in higher intrinsic SPA and protection against DIO. Based on this, we hypothesized that naturally occurring variation in SPA and orexin signaling is sufficient to drive differences in sensitivity to DIO.
  
  
  METHODS
  Orexin expression, behavioral responses to orexin-A, basal energy expenditure and sensitivity to DIO were measured in in non-manipulated male Sprague-Dawley rats selected for high and low intrinsic SPA.
  
  
  RESULTS
  Male Sprague-Dawley rats were classified as high-activity or low-activity based on differences in intrinsic SPA. High-activity rats showed higher expression of prepro-orexin mRNA, higher sensitivity to behavioral effects of orexin injection, higher basal energy expenditure and were more resistant to obesity caused by high-fat diet consumption than low-activity rats.
  
  
  CONCLUSIONS
  Our results define a new model of differential DIO sensitivity, the high-activity and low-activity rats, and suggest that naturally occurring variations in intrinsic SPA cause differences in energy expenditure that are mediated by orexin signaling and alter DIO sensitivity.
authors: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA. perez087@umn.edu
authors: Claudio E
authors: CE
authors: Perez-Leighton
authors: Kelsey
authors: K
authors: Boland
authors: Charles J
authors: CJ
authors: Billington
authors: Catherine M
authors: CM
authors: Kotz
mesh_terms: D000818:Animals; D001947:Breeding; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D000068797:Orexins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D012333:RNA, Messenger
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