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

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: Age; Body mass index (BMI); Energy metabolism; Gender; Muscle of origin; Skeletal muscle cells.

Fig. 1

Cellular energy metabolism presented by gender. a Glucose uptake, b glucose oxidation, c oleic acid uptake, and d oleic acid oxidation in cultured myotubes established from male and female volunteers. Results are presented individually and with mean ± SEM from experiments on myotubes from a, b 80 (49 males and 31 females) participants or c, d 82 (50 males and 32 females) participants

Fig. 2

Cellular energy metabolism presented by donor age. a Glucose uptake, b glucose oxidation, c oleic acid uptake, and d oleic acid oxidation in cultured human myotubes. Results are presented individually from experiments on myotubes from a, b 80 or c, d 82 participants

Fig. 3

Cellular energy metabolism presented by body mass index (BMI) of the donors. a Glucose uptake, b glucose oxidation, c oleic acid uptake, and d oleic acid oxidation in cultured human myotubes. Results are presented individually from experiments on myotubes from a, b 80 or c, d 82 participants

Fig. 4

Cellular energy metabolism presented by the muscle of origin. a Glucose uptake, b glucose oxidation, c oleic acid uptake, and d oleic acid oxidation in cultured myotubes established from three different muscles. Results are presented individually and with mean ± SEM from 80 to 82 individual experiments: a, b 30 or c, d 32 experiments on myotubes from m. obliquus internus abdominis, 35 experiments on myotubes from m. vastus lateralis, and 15 experiments on myotubes from mm. interspinales

Fig. 5

Impact of donor age on cellular mRNA expression of PDK4 and PPARGC1A. Linear regression analysis between donor age and a cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) relative to housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and b cellular mRNA expression of peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) relative to housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0)