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. 2023 Feb 24;14:1098570. doi: 10.3389/fimmu.2023.1098570

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Copyright © 2023 Li, Gao, Sun, Zhang, Yang, Zheng and Shen

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Main signal pathways of Metrnl in myocytes. Metrnl could activate AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-δ (PPAR-γ) signaling by increasing intracellular calcium ion, reactive oxygen species (ROS), or AMP/ATP ratio levels in skeletal muscle cells. Activation of AMPK phosphorylation stimulated phosphorylation of HDAC5 and TBC1DI, both of which resulted in the GLUT4 transcription activation and translocation from the cytoplasm to the membrane. Highly PPAR-γ expressions and AMPK phosphorylation increased fatty acid oxidation, IκBα phosphorylation, and NFκB nuclear translocation. Besides, Metrnl also increased intramuscular PGC-1α and UCPs expressions, thus promoting mitochondria thermogenesis.