Substrate oxidation in primary human skeletal muscle cells is influenced by donor age.

Substrate oxidation in primary human skeletal muscle cells is influenced by donor age.
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DOI:
10.1007/s00441-020-03275-w
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发表时间:
2020-12
影响因子:
3.6
通讯作者:
Lund J
Lund J
中科院分区:
生物学3区
文献类型:
--
作者:
Aas V;Thoresen GH;Rustan AC;Lund J

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原代人肌管是研究与肌肉能量代谢变化相关的人类疾病的替代系统,可以替代完整的骨骼肌。这项工作旨在研究体外人肌管中的脂肪酸和葡萄糖代谢是否与肌肉来源、供体性别、年龄或体重指数(BMI)有关。从3块不同的骨骼肌,即股外侧肌、腹内斜肌和棘间肌,建立了82个供体的肌管,并对细胞能量代谢进行了评估。多元线性回归分析显示,在校正性别、BMI和肌肉来源后,供体年龄对葡萄糖和油酸氧化有显著影响。供体BMI是细胞油酸摄取的唯一显著因素,而细胞葡萄糖摄取不依赖于任何被检查的变量。尽管年龄对底物氧化有影响,但丙酮酸脱氢酶激酶4 (PDK4)和过氧化物酶体增殖物激活受体γ辅助激活因子1 α (PPARGC1A)的细胞mRNA表达与供体年龄无关。总之,供体年龄显著影响培养的人肌管中底物氧化,而供体BMI影响细胞油酸摄取。
Primary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e., musculus vastus lateralis, musculus obliquus internus abdominis, and musculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.
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