title: Sarcolipin trumps β-adrenergic receptor signaling as the favored mechanism for muscle-based diet-induced thermogenesis.
abstract: 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.
authors.affiliation: University of Waterloo, Department of Kinesiology, 200 University Ave. W., ON, Canada N2L 3G1.
authors.forename: Eric
authors.initials: E
authors.lastname: Bombardier
authors.forename: Ian C
authors.initials: IC
authors.lastname: Smith
authors.forename: Daniel
authors.initials: D
authors.lastname: Gamu
authors.forename: Val A
authors.initials: VA
authors.lastname: Fajardo
authors.forename: Chris
authors.initials: C
authors.lastname: Vigna
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Sayer
authors.forename: Subash C
authors.initials: SC
authors.lastname: Gupta
authors.forename: Naresh C
authors.initials: NC
authors.lastname: Bal
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: A Russell
authors.initials: AR
authors.lastname: Tupling
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology*
chemical_list: D009124:Muscle Proteins; D011510:Proteolipids; D011943:Receptors, Adrenergic, beta; C077258:sarcolipin; D002118:Calcium
keywords: calcium cycling; energy expenditure; obesity; skeletal muscle