Paran Christopher W, Verkerke Anthony R P, Heden Timothy D, Park Sanghee, Zou Kai, Lawson Heather A, Song Haowei, Turk John, Houmard Joseph A, Funai Katsuhiko
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
Department of Kinesiology, East Carolina University, Greenville, North Carolina, USA.
Obesity (Silver Spring). 2015 Jul;23(7):1440-9. doi: 10.1002/oby.21123. Epub 2015 May 13.
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.
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.
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.
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.
肌脂蛋白（SLN）通过对肌浆网/内质网Ca(2+) -ATP酶（SERCA）泵的作用来调节肌肉能量消耗。尚不清楚SLN依赖的呼吸作用是否与人类肥胖相关，但全转录组基因表达谱分析显示，严重肥胖（OB）个体的肌细胞中SLN的表达高于瘦对照（LN）个体。本研究的目的是检测LN和OB人群肌肉中SLN依赖的细胞呼吸速率。
从7名LN和OB白种女性的肌肉活检样本中分离出原代肌细胞。在LN和OB肌细胞中，分别在有和没有慢病毒介导的SLN基因敲低的情况下评估细胞呼吸。
与LN细胞相比，OB细胞中SLN mRNA和蛋白丰度更高。尽管野生型OB细胞中SLN水平升高，但与LN相比，OB中SLN缺陷细胞的呼吸速率更高。肥胖引起的SLN依赖呼吸效率降低与肌浆网磷脂组改变有关。
与瘦对照相比，严重肥胖人群肌肉中SLN依赖的呼吸作用降低。确定影响SLN效率的分子机制可能会带来促进骨骼肌能量消耗增加的干预措施。
