2. Academic Validation
  3. Adiponectin upregulates irisin expression through the APPL1/p38MAPK/PGC-1α signalling pathway in murine skeletal muscle

Adiponectin upregulates irisin expression through the APPL1/p38MAPK/PGC-1α signalling pathway in murine skeletal muscle

  • Mol Cell Endocrinol. 2026 Jun:616:112743. doi: 10.1016/j.mce.2026.112743.
Ruiqi Huang 1,  Sitong Xu 2,  Qi Guo 3,  Shicheng Cao 3,  Donghui Tang 4,  Xuejie Yi 5
Affiliations

Affiliations

  • 1 Department of College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, China; Department of School of Physical Education, Liaoning Normal University, Dalian, Liaoning, China.
  • 2 Department of College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, China.
  • 3 Department of School of Intelligent Medicine, China Medical University, Shenyang, China.
  • 4 Department of College of P.E. and Sports, Beijing Normal University, Beijing, China.
  • 5 Department of College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, China. Electronic address: [email protected].
PMID: 41654165 DOI: 10.1016/j.mce.2026.112743
Abstract

Adiponectin and irisin regulate energy homeostasis and interact with Peroxisome Proliferator-activated Receptor coactivator 1α (PGC-1α). However, whether they establish a signal connection via PGC-1α is unclear. In the current study, the expression of irisin was significantly decreased in the skeletal muscle of Adiponectin knockout (KO) mice, accompanied by a de crease in APPL1/p38 mitogen-activated protein kinase (MAPK)/PGC-1α. However, Adiponectin administration reversed this effect. In vitro, the p38 MAPK/PGC-1α signalling pathway mediated adiponectin-induced FNDC5 expression and irisin release in mouse-derived C2C12 myotube cells. Moreover, obesity caused dysregulation of the Adiponectin/APPL1/p38 MAPK/PGC-1α signalling pathway in murine skeletal muscle, ultimately inhibiting irisin synthesis and secretion; meanwhile, prolonged exercise or exogenous recombinant Adiponectin intervention activated this pathway in mouse skeletal muscle. This corresponded with an apparent improvement in high-fat diet-induced Insulin resistance. The effect of mechanically stretching C2C12 myotube cells was consistent with in vivo findings. Hence, Adiponectin upregulates irisin through the APPL1/p38MAPK/PGC-1α signalling pathway in murine skeletal muscle, which may enhance Insulin sensitivity.

Keywords

Adiponectin; C2C12 cell; Insulin resistance; Irisin; Obesity; Skeletal muscle.

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