Energy metabolism in skeletal muscle cells from donors with different body mass index

Parmeshwar B Katare; Andrea Dalmao-Fernandez; Abel M Mengeste; Håvard Hamarsland; Stian Ellefsen; Hege G Bakke; Eili Tranheim Kase; G Hege Thoresen; Arild C Rustan

doi:10.3389/fphys.2022.982842

Energy metabolism in skeletal muscle cells from donors with different body mass index

Front Physiol. 2022 Nov 17:13:982842. doi: 10.3389/fphys.2022.982842. eCollection 2022.

Authors

Parmeshwar B Katare¹, Andrea Dalmao-Fernandez¹, Abel M Mengeste¹, Håvard Hamarsland², Stian Ellefsen², Hege G Bakke¹, Eili Tranheim Kase¹, G Hege Thoresen^{1

3}, Arild C Rustan¹

Affiliations

¹ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Blindern, Norway.
² Faculty of Social and Health Sciences, Section for Health and Exercise Physiology, Inland Norway University of Applied Sciences, Lillehammer, Norway.
³ Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

Obesity and physical inactivity have a profound impact on skeletal muscle metabolism. In the present work, we have investigated differences in protein expression and energy metabolism in primary human skeletal muscle cells established from lean donors (BMI<25 kg/m²) and individuals with obesity (BMI>30 kg/m²). Furthermore, we have studied the effect of fatty acid pretreatment on energy metabolism in myotubes from these donor groups. Alterations in protein expression were investigated using proteomic analysis, and energy metabolism was studied using radiolabeled substrates. Gene Ontology enrichment analysis showed that glycolytic, apoptotic, and hypoxia pathways were upregulated, whereas the pentose phosphate pathway was downregulated in myotubes from donors with obesity compared to myotubes from lean donors. Moreover, fatty acid, glucose, and amino acid uptake were increased in myotubes from individuals with obesity. However, fatty acid oxidation was reduced, glucose oxidation was increased in myotubes from subjects with obesity compared to cells from lean. Pretreatment of myotubes with palmitic acid (PA) or eicosapentaenoic acid (EPA) for 24 h increased glucose oxidation and oleic acid uptake. EPA pretreatment increased the glucose and fatty acid uptake and reduced leucine fractional oxidation in myotubes from donors with obesity. In conclusion, these results suggest that myotubes from individuals with obesity showed increased fatty acid, glucose, and amino acid uptake compared to cells from lean donors. Furthermore, myotubes from individuals with obesity had reduced fatty acid oxidative capacity, increased glucose oxidation, and a higher glycolytic reserve capacity compared to cells from lean donors. Fatty acid pretreatment enhances glucose metabolism, and EPA reduces oleic acid and leucine fractional oxidation in myotubes from donor with obesity, suggesting increased metabolic flexibility after EPA treatment.

Keywords: EPA; eicosapentaenoic acid; metabolism; mitochondria; obesity; skeletal muscle cells.