Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats

C. Shukla, L. G. Koch, S. L. Britton, Minying Cai, Victor J Hruby, M. Bednarek, C. M. Novak

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Physical activity and non-exercise activity thermogenesis (NEAT) are crucial factors accounting for individual differences in body weight, interacting with genetic predisposition. In the brain, a number of neuroendocrine intermediates regulate food intake and energy expenditure (EE); this includes the brain melanocortin (MC) system, consisting of MC peptides as well as their receptors (MCR). MC3R and MC4R have emerged as critical modulators of EE and food intake. To determine how variance in MC signaling may underlie individual differences in physical activity levels, we examined behavioral response to MC receptor agonists and antagonists in rats that show high and low levels of physical activity and NEAT, that is, high- and low-capacity runners (HCR, LCR), developed by artificial selection for differential intrinsic aerobic running capacity. Focusing on the hypothalamus, we identified brain region-specific elevations in expression of MCR 3, 4, and also MC5R, in the highly active, lean HCR relative to the less active and obesity-prone LCR. Further, the differences in activity and associated EE as a result of MCR activation or suppression using specific agonists and antagonists were similarly region-specific and directly corresponded to the differential MCR expression patterns. The agonists and antagonists investigated here did not significantly impact food intake at the doses used, suggesting that the differential pattern of receptor expression may by more meaningful to physical activity than to other aspects of energy balance regulation. Thus, MCR-mediated physical activity may be a key neural mechanism in distinguishing the lean phenotype and a target for enhancing physical activity and NEAT.

Original languageEnglish (US)
Pages (from-to)252-267
Number of pages16
JournalNeuroscience
Volume310
DOIs
StatePublished - Dec 3 2015

Fingerprint

Melanocortin Receptors
Melanocortins
Thermogenesis
Energy Metabolism
Eating
Exercise
Individuality
Brain
Genetic Predisposition to Disease
Energy Intake
Running
Hypothalamus
Obesity
Body Weight
Phenotype
Peptides

Keywords

  • HCR/LCR
  • Non-exercise activity thermogenesis (NEAT)
  • Obesity
  • Spontaneous physical activity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Contribution of regional brain melanocortin receptor subtypes to elevated activity energy expenditure in lean, active rats. / Shukla, C.; Koch, L. G.; Britton, S. L.; Cai, Minying; Hruby, Victor J; Bednarek, M.; Novak, C. M.

In: Neuroscience, Vol. 310, 03.12.2015, p. 252-267.

Research output: Contribution to journalArticle

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