Substrate oxidation in primary human skeletal muscle cells is influenced by donor age
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Substrate oxidation in primary human skeletal muscle cells is influenced by donor age Vigdis Aas 1 & G. Hege Thoresen 2,3 & Arild C. Rustan 2 & Jenny Lund 2 Received: 2 December 2019 / Accepted: 7 August 2020 # The Author(s) 2020
Abstract 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. Keywords Skeletal muscle cells . Energy metabolism . Age . Body mass index (BMI) . Muscle of origin . Gender
Introduction Primary human skeletal muscle cells (myotubes) derived from satellite cells represent an alternative system to intact skeletal muscle that can be used for the study of human diseases related to changes in energy metabolism (Aas et al. 2013; Henry et al. 1995). It has been observed that myotubes display morphological, metabolic, and biochemical similarities to adult skeletal muscle (Gaster et al. 2001; Henry et al. 1995; Thompson et al. 1996). This cell model has the most relevant genetic background, and because these cells are not immortalized, they allow investigation of the innate characteristics of
* Jenny Lund [email protected] 1
Department of Life Sciences and Health, Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo, Norway
2
Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Blindern, P.O. Box 1068, 0316 Oslo, Norway
3
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
the donors from whom the cells were obtained (Aas et al. 2013). In addition, the extracellular environment can be precisely controlled and modulated ex vivo making myotubes a valuable system for research. Cultured human myotubes retain some of the phenotypic traits of their donors. For instance, the diabetic phenotype is conserved in myotubes established from subjects with obesity/ type 2
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