Sarcolipin trumps β-adrenergic receptor signaling as the favored mechanism for muscle-based diet-induced thermogenesis

Sarcolipin (SLN) regulates muscle-based nonshivering thermogenesis and is up-regulated with high-fat feeding (HFF). To investigate whether other muscle-based thermogenic systems compensate for a lack of Sln and to firmly establish SLN as a mediator of diet-induced thermogenesis (DIT), we measured muscle and whole-body energy expenditure in chow- and high-fat-fed Sln−/− and wild-type (WT) mice. Following HFF, resting muscle metabolic rate (Vo2, μl/g/s) was increased similarly in WT (0.28±0.02 vs. 0.31±0.03) and Sln−/− (0.23±0.03 vs. 0.35±0.02) mice due to increased sympathetic nervous system activation in Sln−/− mice; however, whole-body metabolic rate (Vo2, ml/kg/h) was lower in Sln−/− compared with WT mice following HFF but only during periods when the mice were active in their cages (WT, 2894±87 vs. Sln−/−, 2708±61). Treatment with the β-adrenergic receptor (β-AR) antagonist propranolol during HFF completely prevented muscle-based DIT in Sln−/− mice; however, it had no effect in WT mice, resulting in greater differences in whole-body metabolic rate and diet-induced weight gain. Our results suggest that β-AR signaling partially compensates for a lack of SLN to activate muscle-based DIT, but SLN is the primary and more effective mediator.—Bombardier, E., Smith, I. C., Gamu, D., Fajardo, V. A., Vigna, C., Sayer, R. A., Gupta, S. C., Bal, N. C., Periasamy, M., Tupling, A. R. Sarcolipin trumps β-adrenergic receptor signaling as the favored mechanism for muscle-based diet-induced thermogenesis.