Hoxa11 and Hoxa13 facilitate slow-twitch muscle formation in C2C12 cells and indirectly affect the lipid deposition of 3T3-L1 cells.

Abstract

Muscle-fiber type in livestock skeletal muscles influences meat quality, but the underlying mechanisms remain unclear. We previously showed that Homeobox A11 (Hoxa11) and Homeobox A13 (Hoxa13) are differentially expressed in fast- and slow-twitch muscles, but their effects on the formation of muscle-fiber types and intramuscular fat deposition have not been investigated. Here, our results revealed that overexpression of Hoxa11 and Hoxa13 delayed cell-cycle progression in C2C12 myoblasts, reduced their proliferation, and promoted their differentiation into slow-twitch muscle fibers. Knockdown experiments produced the opposite results. The conditioned media of differentiated C2C12 cells with Hoxa11/Hoxa13 overexpression or knockdown were harvested. Staining results showed that adipogenesis of preadipocytes was significantly promoted by Hoxa13 knockdown C2C12 cell culture medium. Changes in lipid accumulation were due to a reduction in lipid decomposition and an increase in triglyceride synthesis; genes related to fatty-acid synthesis were decreased. In conclusion, our study showed that Hoxa11 and Hoxa13 promote slow-twitch muscle formation and indirectly regulate preadipocyte adipogenesis, which may facilitate meat-quality improvement in the future.