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The Effects of Metformin on Skeletal Muscle Differentiation and Satellite Cell Function in C2C12 Myocytes and Juvenile Lean and Obese Mice
Author(s) -
Kinsey Stephen,
Ochab Jess
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r6249
Subject(s) - metformin , ampk , medicine , endocrinology , myocyte , myogenesis , myogenin , skeletal muscle , c2c12 , myod , amp activated protein kinase , chemistry , biology , protein kinase a , insulin , microbiology and biotechnology , kinase
AMP activated protein kinase (AMPK) functions as a cellular energy sensor and it is a target for the treatment of obesity and type II diabetes. Activation of AMPK has well‐known benefits such as increased fuel oxidation and enhanced insulin sensitivity, however, it also may lead to compromised satellite cell function. This may be particularly detrimental to muscle development in juveniles, when satellite cell density and activity is high. In this study, the type II diabetic drug metformin was used to pharmacologically activate AMPK in C2C12 mouse skeletal muscle myoblasts and in juvenile lean and obese mice. In C2C12 cells 48 h of metformin treatment led to increased phosphorylation of AMPK and reduced mitochondrial respiration, as expected. Myocytes treated with metformin had a decreased expression of the myogenic markers, MyoD and myogenin, as well as a reduction in the satellite cell marker Pax7, and the myotubes were smaller in metformin treated cells. Further, nuclear recruitment was reduced in the metformin group, consistent with a reduction in satellite cell fusion with myotubes. In gastrocnemius from juvenile lean and obese mice, 6 weeks of metformin treatment had little effect on myogenic markers or on Pax7. However, nuclear recruitment was reduced in gastrocnemius from both lean and obese mice. These results support the hypothesis that AMPK activation with metformin in cultured muscle cells and juvenile lean and obese mice interferes with satellite cell fusion.