Human HDL subclasses modulate energy metabolism in skeletal muscle cells

Jenny Lund; Emilia Lähteenmäki; Tiia Eklund; Hege G Bakke; G Hege Thoresen; Eija Pirinen; Matti Jauhiainen; Arild C Rustan; Maarit Lehti

doi:10.1016/j.jlr.2023.100481

Human HDL subclasses modulate energy metabolism in skeletal muscle cells

J Lipid Res. 2024 Jan;65(1):100481. doi: 10.1016/j.jlr.2023.100481. Epub 2023 Nov 24.

Authors

Jenny Lund¹, Emilia Lähteenmäki², Tiia Eklund³, Hege G Bakke¹, G Hege Thoresen⁴, Eija Pirinen⁵, Matti Jauhiainen⁶, Arild C Rustan¹, Maarit Lehti⁷

Affiliations

¹ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
² Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland. Electronic address: emilia.i.lahteenmaki@jyu.fi.
³ Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland.
⁴ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway; Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Research Unit for Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland.
⁶ Department of Public Health and Welfare, Minerva Foundation Institute for Medical Research and Finnish Institute for Health and Welfare, Helsinki, Finland.
⁷ Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

Abstract

In addition to its antiatherogenic role, HDL reportedly modulates energy metabolism at the whole-body level. HDL functionality is associated with its structure and composition, and functional activities can differ between HDL subclasses. Therefore, we studied if HDL₂ and HDL₃, the two major HDL subclasses, are able to modulate energy metabolism of skeletal muscle cells. Differentiated mouse and primary human skeletal muscle myotubes were used to investigate the influences of human HDL₂ and HDL₃ on glucose and fatty uptake and oxidation. HDL-induced changes in lipid distribution and mRNA expression of genes related to energy substrate metabolism, mitochondrial function, and HDL receptors were studied with human myotubes. Additionally, we examined the effects of apoA-I and discoidal, reconstituted HDL particles on substrate metabolism. In mouse myotubes, HDL subclasses strongly enhanced glycolysis upon high and low glucose concentrations. HDL₃ caused a minor increase in ATP-linked respiration upon glucose conditioning but HDL₂ improved complex I-mediated mitochondrial respiration upon fatty acid treatment. In human myotubes, glucose metabolism was attenuated but fatty acid uptake and oxidation were markedly increased by both HDL subclasses, which also increased mRNA expression of genes related to fatty acid metabolism and HDL receptors. Finally, both HDL subclasses induced incorporation of oleic acid into different lipid classes. These results, demonstrating that HDL subclasses enhance fatty acid oxidation in human myotubes but improve anaerobic metabolism in mouse myotubes, support the role of HDL as a circulating modulator of energy metabolism. Exact mechanisms and components of HDL causing the change, require further investigation.

Keywords: HDL subclasses; cellular respiration; fatty acid/transport; glucose; glycolysis; lipoproteins/metabolism; lipoproteins/receptors; mitochondria; oxidative phosphorylation; skeletal muscle myotubes; substrate oxidation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Energy Metabolism
Fatty Acids / metabolism
Glucose / metabolism
Humans
Mice
Muscle Fibers, Skeletal* / metabolism
Muscle, Skeletal* / metabolism
RNA, Messenger / metabolism

Substances

Fatty Acids
Glucose
RNA, Messenger