Reduced efficiency of sarcolipin-dependent respiration in myocytes from humans with severe obesity.

Abstract

OBJECTIVE:

Sarcolipin (SLN) regulates muscle energy expenditure through its action on sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump. It is unknown whether SLN-dependent respiration has relevance to human obesity, but whole-transcriptome gene expression profiling revealed that SLN was more highly expressed in myocytes from individuals with severe obesity (OB) than in lean controls (LN). The purpose of this study was to examine SLN-dependent cellular respiratory rates in LN and OB human muscles.

METHODS:

Primary myocytes were isolated from muscle biopsy from seven LN and OB Caucasian females. Cellular respiration was assessed with and without lentivirus-mediated SLN knockdown in LN and OB myocytes.

RESULTS:

SLN mRNA and protein abundance was greater in OB compared to LN cells. Despite elevated SLN levels in wild-type OB cells, respiratory rates among SLN-deficient cells were higher in OB compared to LN. Obesity-induced reduction in efficiency of SLN-dependent respiration was associated with altered sarcoplasmic reticulum phospholipidome.

CONCLUSIONS:

SLN-dependent respiration is reduced in muscles from humans with severe obesity compared to lean controls. Identification of the molecular mechanism that affects SLN efficiency might lead to interventions that promote an increase in skeletal muscle energy expenditure.

• Authors: Christopher W Paran, Anthony R P Verkerke, Timothy D Heden, Sanghee Park, Kai Zou, Heather A Lawson, Haowei Song, John Turk, Joseph A Houmard, Katsuhiko Funai
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 23 Issue 7 Pg. 1440-9 (Jul 2015) ISSN: 1930-739X [Electronic] United States
• PMID: 25970801 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Obesity Society.

Chemical References

• Muscle Proteins
• Proteolipids
• sarcolipin
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• Energy Metabolism (physiology)
• Female
• Humans
• Muscle Cells (metabolism)
• Muscle Proteins (metabolism)
• Muscle, Skeletal (metabolism)
• Obesity, Morbid (metabolism)
• Proteolipids (metabolism)
• Sarcoplasmic Reticulum (metabolism)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)