A possibility of uncoupling protein 1 induction with the enhancement of myogenesis related to ruminal fermentation.

The expression of uncoupling protein 1 (UCP1), which regulates energy expenditure, is limited to brown/beige adipocytes in most mammals; however, it is also detected in the skeletal muscles of cattle. We previously observed a positive relationship between Ucp1 and fast-twitch myosin heavy chain (Myh) expression in bovine skeletal muscles. In the present study, we explored the regulatory expression of Ucp1 in bovine myogenic cells using cell culture. Vitamin C and high-dose capsaicin, which induce the formation of fast-twitch myotubes in murine myogenic cells, did not stimulate myogenesis in bovine myosatellite cells. Treatment with 4-phenylbutyric acid (PBA), a histone deacetylase inhibitor that enhances histone acetylation, upregulates the expression of all myogenic regulatory factors (MRFs), except Myog, in bovine myogenic cells. Consistent with this, PBA increased the expression levels of acetylated lysine 27 of histone 3 (H3K27), the fast-twitch component MYH1/2, and Ucp1 in bovine myogenic cells. SB203580, an inhibitor of p38 MAP kinase, blocked PBA-induced myogenesis and Ucp1 upregulation. PBA is a butyric acid-related molecule, and cattle produce large amounts of volatile fatty acids (VFAs), including acetic acid, propionic acid, and butyric acid, through ruminal fermentation. Propionic acid treatment stimulated H3K27 acetylation, myogenesis, and Ucp1 induction. Thus, the upregulation of muscular Ucp1 may be related to myogenic stimulation through the modulation of histone acetylation status in cattle; we propose that the cattle-specific expression of muscular UCP1 results from VFA production through ruminal fermentation.