Effects of HOXC8 on the Proliferation and Differentiation of Porcine Preadipocytes

SIMPLE SUMMARY: Fat accumulation is important for both livestock production and human health. Previous studies provide a clue to the involvement of Homeobox C8 (HOXC8) in adipogenesis. Here, we make clear that porcine HOXC8 promotes the proliferation and differentiation of preadipocytes through gain- and loss-of-function approaches. Furthermore, the genes and pathways affected by HOXC8 during the regulation of preadipocyte proliferation and differentiation are identified. The results provide new data for the clarification of mechanisms underlying fat accumulation, which is the basis for controlling fat contents in mammals. ABSTRACT: Transcription factor Homeobox C8 (HOXC8) is identified as a white adipose gene as revealed by expression profile analysis in fat tissues. However, the specific role of HOXC8 in fat accumulation remains to be identified. This study was designed to reveal the effects of HOXC8 on preadipocyte proliferation and differentiation. We first make clear that the expression of HOXC8 is associated with fat contents in muscles, highlighting a role of HOXC8 in fat accumulation. Next, it is demonstrated that HOXC8 promotes the proliferation and differentiation of preadipocytes through gain- and loss-of-function assays in primary cultured porcine preadipocytes. Then, mechanisms underlying the regulation of HOXC8 on preadipocyte proliferation and differentiation are identified with RNA sequencing, and a number of differentially expressed genes (DEGs) in response to HOXC8 knockdown are identified. The top GO (Gene Ontology) terms enriched by DEGs involved in proliferation and differentiation, respectively, are identical. IL-17 signaling pathway is the common one significantly enriched by DEGs involved in preadipocyte proliferation and differentiation, respectively, indicating its importance in mediating fat accumulation regulated by HOXC8. Additionally, we find that the inhibition of proliferation is one of the main processes during preadipocyte differentiation. The results will contribue to further revealing the mechanisms underlying fat accumulation regulated by HOXC8.