Regulatory Expression Of Uncoupling Protein 1 And Its Related Genes By Endogenous Activity Of The Transforming Growth Factor-Beta Family In Bovine Myogenic Cells

Uncoupling protein 1 (UCP1) is responsible for non-shivering thermogenesis, with restricted expression in brown/beige adipocytes in humans and rodents. We have previously shown an unexpected expression of UCP1 in bovine skeletal muscles. This study evaluated factors affectingUcp1gene expression in cultured bovine myogenic cells. Myosatellite cells, which were isolated from the bovinemusculus longissimus cervicis, were induced to differentiate into myotubes in the presence of 2% horse serum. Previous studies using murine brown/beige adipocytes revealed thatUcp1expression levels are directly increased by forskolin and all-transretinoic acid (RA). The transforming growth factor-beta (TGF-beta)/activin pathway negatively regulatedUcp1expression, whereas activation of the bone morphogenetic protein (BMP) pathway indirectly increasesUcp1expression through the stimulation of brown/beige adipogenesis. Neither forskolin nor RA significantly affectedUcp1mRNA levels in bovine myogenic cells. A-83-01, an inhibitor of the TGF-beta/activin pathway, stimulated myogenesis in these cells. A-83-01 significantly increased the expression of some brown fat signature genes such asPgc-1 alpha,Cox7a1, andDio2, with a quantitative but not significant increase in the expression ofUcp1. Treatment with LDN-193189, an inhibitor of the BMP pathway, did not affect the differentiation of bovine myosatellite cells. Rather, LDN-193189 increasedUcp1mRNA levels without modulating the levels of other brown/beige adipocyte-related genes. The current results indicate that the regulation ofUcp1expression in bovine myogenic cells is distinct from that in murine brown/beige adipocytes, which has been more intensely characterized.Significance of the studyWe previously reported unexpected expression of Ucp1 in bovine muscle tissues; Ucp1 expression has been known to be detected predominantly in brown/beige adipocytes. This study examined regulatory expression of bovine Ucp1 in myogenic cells. Consistent with the changes in expression levels of brown/beige adipocyte-selective genes, Ucp1 expression tended to be increased by inhibition of endogenous TGF-beta activity. In contrast, inhibition of endogenous BMP significantly increased Ucp1 expression without affecting brown/beige adipocyte-selective gene expression. The current results indicate that regulatory expression of Ucp1 in bovine myogenic cells is distinct from that in murine brown/beige adipocytes that is more intensely characterized.