Apigenin enhances skeletal muscle hypertrophy and myoblast differentiation by regulating Prmt7

Abstract

Apigenin, a natural flavone abundant in various plant-derived foods including parsley and celery, has been shown to prevent inflammation and inflammatory diseases. However, the effect of apigenin on skeletal muscle hypertrophy and myogenic differentiation has not previously been elucidated. Here, we investigated the effects of apigenin on quadricep muscle weight and running distance using C57BL/6 mice on an accelerating treadmill. Apigenin stimulated mRNA expression of MHC (myosin heavy chain) 1, MHC2A, and MHC2B in the quadricep muscles of these animals. GPR56 (G protein-coupled receptor 56) and its ligand collagen III were upregulated by apigenin supplementation, together with enhanced PGC-1α, PGC-1α1, PGC-1α4, IGF1, and IGF2 expression. Prmt7 protein expression increased in conjunction with Akt and mTORC1 activation. Apigenin treatment also upregulated FNDC5 (fibronectin type III domain containing 5) mRNA expression and serum irisin levels. Furthermore, apigenin stimulated C2C12 myogenic differentiation and upregulated total MHC, MHC2A, and MHC2B expression. These events were attributable to an increase in Prmt7-p38-myoD expression and Akt and S6K1 phosphorylation. We also observed that Prmt7 regulates both PGC-1α1 and PGC-1α4 expression, resulting in a subsequent increase in GPR56 expression and mTORC1 activation. Taken together, these findings suggest that apigenin supplementation can promote skeletal muscle hypertrophy and myogenic differentiation by regulating the Prmt7-PGC-1α-GPR56 pathway, as well as the Prmt7-p38-myoD pathway, which may contribute toward the prevention of skeletal muscle weakness.

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

“…The myogenic marker gene Myog significantly interacted with two potential cis regulatory elements at 40 and 80 kb upstream ( Figure 8 B, Table S5 ). Moreover, Igf2 , which regulates skeletal muscle development 13 , 46 , was also found to exhibit higher interaction with imprinted Igf2 / H19 in myotubes than in myoblasts ( Table S5 ).…”

“…Adipogenic differentiation and myogenic differentiation are essential developmental processes of adipose and skeletal muscle, regulated by complex molecular networks and epigenetic modifications 8 - 11 . Adipogenesis and myogenesis marker genes (e.g., PPARG , CEBPA , and FABP4 in adipocytes, and MRFs and MHC in myotubes) were shown to be activated during differentiation, accompanied by changes in cell morphology (lipid droplet accumulation of adipocytes and fusion of myoblasts into multinucleated myotubes, respectively) 12 , 13 . Adipogenesis- and myogenesis-associated expression of PPARG and FRG1 was found to be regulated by long-range chromatin interactions, respectively, suggesting the modulatory role of spatial chromatin structure in adipogenesis and myogenesis 14 , 15 .…”

Induction of Neuronal Differentiation of Murine N2a Cells by Two Polyphenols Present in the Mediterranean Diet Mimicking Neurotrophins Activities: Resveratrol and Apigenin

“…With resveratrol, pro-differentiating activities have also been shown on myoblasts, resulting in the formation of myotubes [ 57 ]. Apigenin has also been shown to promote osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways [ 58 , 59 ], to enhance myoblast differentiation by regulating Prmt7 [ 60 ], to induce granulocytic differentiation in human promyelocytic leukemia HL-60 cells [ 61 ], and to activate morphological differentiation and G2-M arrest in rat neuronal cells [ 62 ]. It has also been reported that apigenin from Croton betulaster Mull inhibits proliferation, induces differentiation and regulates the inflammatory profile of C6 glioma cells [ 63 ].…”

Celery and Celeriac: A Critical View on Present and Future Breeding

“…Apigenin is a flavonoid abundantly available in Apium leaves. It reportedly has anti-cancer properties [reviewed by Kowalczyk et al (2017)] and can enhance skeletal muscle hypertrophy and myoblast differentiation in mice (Jang et al, 2017). As aforementioned, the enzyme responsible for conversion of naringenin to apigenin is known and its manipulation leads to an increased level of apigenin (Tan et al, 2017).…”