Sarcolipin Is a Key Determinant of the Basal Metabolic Rate, and Its Overexpression Enhances Energy Expenditure and Resistance against Diet-induced Obesity.

Abstract

Sarcolipin (SLN) is a novel regulator of sarcoplasmic reticulum Ca(2+) ATPase (SERCA) in muscle. SLN binding to SERCA uncouples Ca(2+) transport from ATP hydrolysis. By this mechanism, SLN promotes the futile cycling of SERCA, contributing to muscle heat production. We recently showed that SLN plays an important role in cold- and diet-induced thermogenesis. However, the detailed mechanism of how SLN regulates muscle metabolism remains unclear. In this study, we used both SLN knockout (Sln(-/-)) and skeletal muscle-specific SLN overexpression (Sln(OE)) mice to explore energy metabolism by pair feeding (fixed calories) and high-fat diet feeding (ad libitum). Our results show that, upon pair feeding, Sln(OE) mice lost weight compared with the WT, but Sln(-/-) mice gained weight. Interestingly, when fed with a high-fat diet, Sln(OE) mice consumed more calories but gained less weight and maintained a normal metabolic profile in comparison with WT and Sln(-/-) mice. We found that oxygen consumption and fatty acid oxidation were increased markedly in Sln(OE) mice. There was also an increase in both mitochondrial number and size in Sln(OE) muscle, together with increased expression of peroxisome proliferator-activated receptor δ (PPARδ) and PPAR γ coactivator 1 α (PGC1α), key transcriptional activators of mitochondrial biogenesis and enzymes involved in oxidative metabolism. These results, taken together, establish an important role for SLN in muscle metabolism and energy expenditure. On the basis of these data we propose that SLN is a novel target for enhancing whole-body energy expenditure.

• Authors: Santosh K Maurya, Naresh C Bal, Danesh H Sopariwala, Meghna Pant, Leslie A Rowland, Sana A Shaikh, Muthu Periasamy
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 17 Pg. 10840-9 (Apr 24 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 25713078 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Fatty Acids
• Muscle Proteins
• PPAR delta
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Proteolipids
• Receptors, Adrenergic, beta-2
• Transcription Factors
• sarcolipin
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• Adipose Tissue, White (metabolism, pathology)
• Animals
• Basal Metabolism (physiology)
• Diet, High-Fat (adverse effects)
• Energy Intake
• Energy Metabolism (physiology)
• Fatty Acids (metabolism)
• Humans
• Mice
• Mice, Knockout
• Mice, Transgenic
• Models, Biological
• Muscle Proteins (deficiency, genetics, metabolism)
• Muscle, Skeletal (metabolism)
• Obesity (etiology, metabolism, prevention & control)
• Oxidation-Reduction
• Oxygen Consumption
• PPAR delta (metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Proteolipids (deficiency, genetics, metabolism)
• Receptors, Adrenergic, beta-2 (metabolism)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
• Transcription Factors (metabolism)
• Up-Regulation
• Weight Loss