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Obesity (Silver Spring). 2018 May;26(5):885-894. doi: 10.1002/oby.22166. Epub 2018 Mar 22.

Inherently Lean Rats Have Enhanced Activity and Skeletal Muscle Response to Central Melanocortin Receptors.

Author information

1
School of Biomedical Sciences, Kent State University, Kent, Ohio, USA.
2
Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
3
Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA.
4
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
5
Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
6
Department of Biological Sciences, Kent State University, Kent, Ohio, USA.

Abstract

OBJECTIVE:

Activity thermogenesis and energy expenditure (EE) are elevated in intrinsically lean rats (high-capacity runners [HCR]) and are also stimulated by melanocortin receptor activation in the ventromedial hypothalamus (VMH). This study determined whether HCR are more responsive to central modulation of activity EE compared with low-capacity runners (LCR).

METHODS:

HCR and LCR rats received intra-VMH microinjections of melanotan II (MTII), a mixed melanocortin receptor agonist. Changes in EE, respiratory exchange ratio, activity EE, muscle heat, norepinephrine turnover, and muscle energetic modulators were compared.

RESULTS:

HCR were significantly more responsive to intra-VMH MTII-induced changes in EE, activity EE, norepinephrine turnover to some muscle subgroups, and muscle mRNA expression of some energetic modulators. Though HCR had high muscle activity thermogenesis, limited MTII-induced modulation of muscle thermogenesis during activity was seen in LCR only.

CONCLUSIONS:

An inherently lean, high-capacity rat phenotype showed elevated response to central melanocortin stimulation of activity EE and use of fat as fuel. This may be driven by sympathetic outflow to skeletal muscle, which was elevated after MTII. Central melanocortin receptor activation also altered skeletal muscle energetic modulators in a manner consistent with elevated EE and lowered respiratory exchange ratio.

PMID:
29566460
PMCID:
PMC5916025
DOI:
10.1002/oby.22166
[Indexed for MEDLINE]
Free PMC Article

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