A1 Journal article (refereed)
Human HDL subclasses modulate energy metabolism in skeletal muscle cells (2024)


Lund, J., Lähteenmäki, E., Eklund, T., Bakke, H. G., Thoresen, G. H., Pirinen, E., Jauhiainen, M., Rustan, A. C., & Lehti, M. (2024). Human HDL subclasses modulate energy metabolism in skeletal muscle cells. Journal of Lipid Research, 65(1), Article 100481. https://doi.org/10.1016/j.jlr.2023.100481


JYU authors or editors


Publication details

All authors or editorsLund, Jenny; Lähteenmäki, Emilia; Eklund, Tiia; Bakke, Hege G.; Thoresen, G. Hege; Pirinen, Eija; Jauhiainen, Matti; Rustan, Arild C.; Lehti, Maarit

Journal or seriesJournal of Lipid Research

ISSN0022-2275

eISSN1539-7262

Publication year2024

Publication date24/11/2023

Volume65

Issue number1

Article number100481

PublisherElsevier

Publication countryUnited States

Publication languageEnglish

DOIhttps://doi.org/10.1016/j.jlr.2023.100481

Publication open accessOpenly available

Publication channel open accessOpen Access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/92559


Abstract

In addition to its anti-atherogenic 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 (d-rHDLs) 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.


Keywordsglucosemitochondriaglucose metabolismfatty acidslipoproteinsmetabolism

Free keywordscellular respiration; substrate oxidation; glycolysis; oxidative phosphorylation; skeletal muscle myotubes; HDL subclasses; fatty acid/transport; glucose; lipoproteins/metabolism; mitochondria; lipoproteins/receptors


Contributing organizations


Ministry reportingYes

VIRTA submission year2023

Preliminary JUFO rating1


Last updated on 2024-03-07 at 01:05