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

Vigdis Aas,Arild C Rustan,Jenny Lund,G Hege Thoresen

doi:10.1007/s00441-020-03275-w

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.

Highlights

Primary human skeletal muscle cells 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)
Energy metabolism in cultured cells was related to donor characteristics from five different myotube cohorts, established from satellite cells isolated from biopsies from three different skeletal muscles, from healthy male and female donors, with varying age and body mass index (BMI) (Table 1)
Cellular energy metabolism parameters presented by gender, donor age, body mass index, and muscle of origin

Summary

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 Cultured human myotubes retain some of the phenotypic traits of their donors. In addition to the genetic background, epigenetic mechanisms are probably involved in retaining the in vivo characteristics of the donors in the cultured cells (Aas et al 2013; Lund et al 2017)

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