Cold exposure alters lipid metabolism of skeletal muscle through HIF-1α-induced mitophagy.

Publisher: BioMed Central Country of Publication: England NLM ID: 101190720 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7007 (Electronic) Linking ISSN: 17417007 NLM ISO Abbreviation: BMC Biol Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2003-

Lipid Metabolism* ; Mitophagy*; Animals ; Mice ; Fatty Acids/metabolism ; Glucose/metabolism ; Lipids ; Muscle, Skeletal/metabolism ; Cold Temperature

Background: In addition to its contractile properties and role in movement, skeletal muscle plays an important function in regulating whole-body glucose and lipid metabolism. A central component of such regulation is mitochondria, whose quality and function are essential in maintaining proper metabolic homeostasis, with defects in processes such as autophagy and mitophagy involved in mitochondria quality control impairing skeletal muscle mass and function, and potentially leading to a number of associated diseases. Cold exposure has been reported to markedly induce metabolic remodeling and enhance insulin sensitivity in the whole body by regulating mitochondrial biogenesis. However, changes in lipid metabolism and lipidomic profiles in skeletal muscle in response to cold exposure are unclear. Here, we generated lipidomic or transcriptome profiles of mouse skeletal muscle following cold induction, to dissect the molecular mechanisms regulating lipid metabolism upon acute cold treatment.
Results: Our results indicated that short-term cold exposure (3 days) can lead to a significant increase in intramuscular fat deposition. Lipidomic analyses revealed that a cold challenge altered the overall lipid composition by increasing the content of triglyceride (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), while decreasing sphingomyelin (SM), validating lipid remodeling during the cold environment. In addition, RNA-seq and qPCR analysis showed that cold exposure promoted the expression of genes related to lipolysis and fatty acid biosynthesis. These marked changes in metabolic effects were associated with mitophagy and muscle signaling pathways, which were accompanied by increased TG deposition and impaired fatty acid oxidation. Mechanistically, HIF-1α signaling was highly activated in response to the cold challenge, which may contribute to intramuscular fat deposition and enhanced mitophagy in a cold environment.
Conclusions: Overall, our data revealed the adaptive changes of skeletal muscle associated with lipidomic and transcriptomic profiles upon cold exposure. We described the significant alterations in the composition of specific lipid species and expression of genes involved in glucose and fatty acid metabolism. Cold-mediated mitophagy may play a critical role in modulating lipid metabolism in skeletal muscle, which is precisely regulated by HIF-1α signaling.
(© 2023. The Author(s).)

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2018YFA0800403 National Key R&D Program of China; 226-2022-00113 Fundamental Research Funds for the Central University

Keywords: Cold exposure; Lipid remodeling; Lipidomic; Mitophagy; Skeletal muscle; Transcriptome

0 (Fatty Acids)
IY9XDZ35W2 (Glucose)
0 (Lipids)

Date Created: 20230208 Date Completed: 20230213 Latest Revision: 20230223

20240829

PMC9906913

10.1186/s12915-023-01514-4

36750818