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

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.