Femoral Artery Infusion of αMSH Increases Muscle Thermogenesis and Promotes Glucose Uptake in Ovariectomized Ewes

The melanocortin system is fundamental to neural control of energy balance and long-term weight regulation. Recent evidence shows that melanocortins also act at peripheral tissues to regulate metabolism, independent of the brain or the sympathetic nervous system (SNS). One such target is skeletal muscle, which contributes to energy expenditure through changes in adaptive thermogenesis. We aimed to determine 1) whether direct femoral infusion of α-melanocyte-stimulating hormone (αMSH) could increase muscle heat production independent of SNS activation and 2) if αMSH-induced skeletal muscle heat production was associated with altered mitochondrial function. Dataloggers were implanted into one hind leg of ovariectomized ewes and set to record vastus lateralis temperature every 15 minutes. A cannula was inserted into one femoral artery for infusion of either αMSH (0.1 µg/h) or saline. Femoral infusion of αMSH increased (P < .0001) skeletal muscle heat production, without effect on food intake. State 4 respiration increased (P < .05) and the respiratory control ratio decreased (P < .05) in mitochondria isolated from αMSH-treated animals. In addition, femoral infusion of αMSH reduced plasma glucose concentration in the femoral, but not the jugular vein; there was no effect of αMSH treatment on nonesterified fatty acid concentrations. These data suggest that αMSH can act locally to increase glucose uptake. We further show that blockade of the α- and β-adrenergic limbs of the SNS with either phentolamine or propranolol infusion had no effect on αMSH-induced skeletal muscle heat production. Overall, we show that αMSH acts directly at skeletal muscle to promote glucose uptake and increase energy expenditure via mitochondrial thermogenesis.