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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Peroxisome Proliferator-Activated Receptor Delta Regulates Myogenic Differentiation via Lipid Droplet-Associated
Rumana Mahzabin1, Md Rezwanul Habib1, Yukako Tokutake2
1Graduate School of Medicine, Science and Technology, Shinshu University, Nagano, Japan.
Abstract:
Skeletal muscle development and metabolic regulation are critical for livestock productivity and meat quality. This study investigated the role of peroxisome proliferator-activated receptor delta (PPARδ) in myogenic differentiation and lipid droplet (LD) formation, focusing in particular on p38 mitogen-activated protein kinase (MAPK) signaling. C2C12 myoblasts were induced to differentiate and treated with the PPARδ agonist GW501516 or antagonist GSK3787. Myogenic differentiation was then assessed via myosin heavy chain immunostaining and calculation of the fusion index and myotube area. LD formation was evaluated by BODIPY staining and analysis of Plin2 expression. Activation of p38 MAPK was analyzed via Western blotting, and its role was examined using the inhibitor SB203580. Activation of PPARδ significantly enhanced myogenic differentiation, whereas its inhibition suppressed this process. PPARδ activation also promoted LD formation and upregulated Plin2 expression during early differentiation. In addition, GW501516 increased p38 MAPK phosphorylation. Inhibition of p38 MAPK markedly attenuated both LD formation and myogenic differentiation induced by PPARδ activation. These findings demonstrate that PPARδ promotes myogenic differentiation through coordinated lipid metabolic remodeling and p38 MAPK signaling, highlighting an association between metabolic regulation and muscle differentiation. This pathway may represent a potential target for improving muscle development and meat quality in livestock.
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