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 of Sln^–/– 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 cytochrome c (+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 & NOTEWORTHY Sarcolipin (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.

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