Liang Yu-Cheng, Cheng Kai-Pi, Kuo Hsin-Yu, Wang Chung-Teng, Chou Hsuan-Wen, Huang Kuan-Lin, Wu Hung-Tsung, Ou Horng-Yih
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Biomedicines. 2023 Oct 5;11(10):2708. doi: 10.3390/biomedicines11102708.
Although obese sarcopenia is a major public health problem with increasing prevalence worldwide, the factors that contribute to the development of obese sarcopenia are still obscure. In order to clarify this issue, a high-fat-diet-induced obese sarcopenia mouse model was utilized. After being fed with a high-fat diet for 24 weeks, decreased motor functions and muscle mass ratios were found in the C57BL/6 mice. In addition, the expression of calsarcin-2 was significantly increased in their skeletal muscle, which was determined by a microarray analysis. In order to clarify the role of calsarcin-2 in muscle, lentiviral vectors containing the calsarcin-2 gene or short hairpin RNA targeted to calsarcin-2 were used to manipulate calsarcin-2 expressions in L6 myoblasts. We found that an overexpression of calsarcin-2 facilitated L6 myoblast differentiation, whereas a calsarcin-2 knockdown delayed myoblast differentiation, as determined by the expression of myogenin. However, the calsarcin-2 knockdown showed no significant effects on myoblast proliferation. In addition, to clarify the relationship between serum calsarcin-2 and sarcopenia, the bilateral gastrocnemius muscle mass per body weight in mice and appendicular skeletal muscle mass index in humans were measured. Although calsarcin-2 facilitated myoblast differentiation, the serum calsarcin-2 concentration was negatively related to skeletal muscle mass index in mice and human subjects. Taken together, calsarcin-2 might facilitate myoblast differentiation and appear to play a compensatory role in sarcopenia.
尽管肥胖性肌肉减少症是一个日益严重的全球公共卫生问题，但其发病因素仍不清楚。为了阐明这一问题，利用了高脂饮食诱导的肥胖性肌肉减少症小鼠模型。给C57BL/6小鼠喂食高脂饮食24周后，发现其运动功能和肌肉质量比下降。此外，通过微阵列分析确定，其骨骼肌中钙肌钙蛋白-2的表达显著增加。为了阐明钙肌钙蛋白-2在肌肉中的作用，使用含有钙肌钙蛋白-2基因的慢病毒载体或靶向钙肌钙蛋白-2的短发夹RNA来调控L6成肌细胞中钙肌钙蛋白-2的表达。我们发现，如通过肌细胞生成素的表达所确定的，钙肌钙蛋白-2的过表达促进了L6成肌细胞的分化，而钙肌钙蛋白-2的敲低则延迟了成肌细胞的分化。然而，钙肌钙蛋白-2的敲低对成肌细胞增殖没有显著影响。此外，为了阐明血清钙肌钙蛋白-2与肌肉减少症之间的关系，测量了小鼠的双侧腓肠肌体重和人类的四肢骨骼肌质量指数。尽管钙肌钙蛋白-2促进了成肌细胞的分化，但血清钙肌钙蛋白-2浓度与小鼠和人类受试者的骨骼肌质量指数呈负相关。综上所述，钙肌钙蛋白-2可能促进成肌细胞分化，并似乎在肌肉减少症中发挥代偿作用。
