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Reduced lipid and glucose oxidation and reduced lipid synthesis in AMPKα2-/- myotubes

C. Skagen, S. Stevanovic, HG. Bakke, TA. Nyman, M. Stensland, ET. Kase, O. Horakova, AC. Rustan, GH. Thoresen

. 2025 ; 131 (3) : 483-492. [pub] 20250109

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc25015572

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from AMPKα2+/+ and AMPKα2-/- mice. Myotubes from AMPKα2-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes from AMPKα2+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleic acid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2-/- mice. Proteomics analysis revealed that AMPKα2-/- myotubes had upregulated pathways related to mitochondrial function and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. In conclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basal oxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial function and fatty acid oxidation and reduced lipid formation.

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$a Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from AMPKα2+/+ and AMPKα2-/- mice. Myotubes from AMPKα2-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes from AMPKα2+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleic acid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2-/- mice. Proteomics analysis revealed that AMPKα2-/- myotubes had upregulated pathways related to mitochondrial function and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. In conclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basal oxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial function and fatty acid oxidation and reduced lipid formation.
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$a Stevanovic, Stanislava $u Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway
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$a Bakke, Hege Gilbø $u Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway
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$a Nyman, Tuula A $u Department of Immunology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Norway
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$a Stensland, Maria $u Department of Immunology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Norway
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$a Kase, Eili Tranheim $u Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway
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$a Horakova, Olga $u Laboratory of Adipose Tissue Biology, Institute of Physiology, of the Czech Academy of Sciences, Prague, Czech Republic
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$a Rustan, Arild C $u Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway
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