Sarcolipin expression is not required for the mitochondrial enzymatic response to physical activity or diet.
In mice, transgenic manipulation of Ca2+-handling proteins is sufficient to alter the metabolic phenotype of muscle. We have previously shown that ablation of sarcolipin (SLN), a regulatory protein and uncoupler of sarco(endo)plasmic reticulum Ca2+-ATPases, leads to excessive diet-induced obesity and glucose intolerance in mice. However, it is unclear how loss of SLN per se affects muscle oxidative capacity and the ability of mitochondria to adapt to physiological stimuli, such as exercise training or calorie overload. To address this question,Sln-/-and wild-type (WT) littermates were given access to voluntary running wheels or underwent a treadmill training protocol for 8 wk. Furthermore, a separate group of mice were given a high-fat diet (42% kcal from fat for 8 wk) to determine whether the excessively obese phenotype ofSln-/-mice is associated with altered oxidative capacity. While voluntary running was insufficient to elicit mitochondrial adaptations, treadmill-trained mice showed significant increases (P< 0.05) in the maximal activities of succinate dehydrogenase (+11%), citrate synthase (+12%), cytochrome oxidase (COX: +17%), along with increased protein expression of cytochromec(+34%) and COX IV (+28%), which were irrespective of SLN expression. Lastly, no changes in the activities of mitochondrial marker enzymes existed with high-fat feeding, regardless of genotype. Together, these findings indicate that SLN is not required for the regulation of oxidative capacity in response to physiological stress, namely exercise or caloric surfeit.NEW & NOTEWORTHYSarcolipin (SLN) has gained considerable attention for its uncoupling role of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). Because of SLN's ability to alter both cellular energy use and cytosolic [Ca2+], the potential exists for a regulatory role of mitochondrial biogenesis. Herein, we show skeletal muscle oxidative capacity to be unaltered in mice lacking SLN following exercise training or high-fat feeding. Our results contrast with published studies of SLN-overexpressing mice, possibly owing to supraphysiological uncoupling of SERCA.
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Daniel
D
Gamu
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Anton
A
Trinh
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Val A
VA
Fajardo
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Eric
E
Bombardier
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada rtupling@uwaterloo.ca.
A Russell
AR
Tupling
D000818:Animals; D002118:Calcium / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D002149:Energy Intake / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011510:Proteolipids / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
D009124:Muscle Proteins; D011510:Proteolipids; C077258:sarcolipin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
Ca2+ handling; SERCA; oxidative capacity; sarcolipin