Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling

This study aimed to determine whether post-prandial temperature excursions in skeletal muscle are consistent with thermogenesis or altered blood flow. Temperature probes were implanted into the vastus lateralis muscle of ovariectomized ewes and blood flow was assessed using laser Doppler flowmetry (tissue flow) and transit-time ultrasound flowmetry (femoral artery flow). The animals were program-fed between 1100 and 1600h and temperature and blood flow were measured during iv administration of either isoprenaline or phenylephrine and during feeding and meal anticipation. In addition, muscle biopsies were collected pre- and post-feeding to measure uncoupling protein (UCP) expression and mitochondrial function as well as indices of calcium cycling (ryanodine 1 receptor: RyR1 and sarco/endoplasmic calcium dependent ATPases SERCA1/ SERCA2a). Isoprenaline increased femoral artery blood flow, whereas phenylephrine reduced blood flow. At high doses only, isoprenaline treatment increased heat production in muscle. Phenylephrine treatment did not alter muscle temperature. Meal anticipation was evoked in fasted animals (previously program-fed) that were housed beside animals that were fed. Increases in muscle temperature were elicited by feeding and meal anticipation, without changes in blood flow during either paradigm. Analyses of respiration in isolated mitochondria indicated that the post-prandial increase in heat production was associated with an increasein state 4 respiration, without increased UCP1, 2 or 3 expression. Feeding increased the expression of RyR1 and SERCA2a. We conclude that excursions in muscle temperature may occur independent of blood flow, suggesting that post-prandial heat production is driven by altered mitochondrial function and changes in calcium cycling.