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Obesity (Silver Spring). 2015 Jul;23(7):1440-9. doi: 10.1002/oby.21123. Epub 2015 May 13.

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

Author information

1
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
2
Department of Kinesiology, East Carolina University, Greenville, North Carolina, USA.
3
Department of Physiology, East Carolina University, Greenville, North Carolina, USA.
4
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
5
Medicine Mass Spectrometry Facility, Washington University School of Medicine, St. Louis, Missouri, USA.

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.

PMID:
25970801
PMCID:
PMC4483165
DOI:
10.1002/oby.21123
[Indexed for MEDLINE]
Free PMC Article

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