HOXA5 Targets ABCD1 and IRF7 to Regulate the Proliferation and Differentiation of Goat Intramuscular Preadipocytes

Intramuscular fat (IMF) is crucial for goat meat quality, being influenced by preadipocyte proliferation and differentiation. Although the developmental transcription factor HOXA5 is associated with adipose tissue development and lipid deposition in mice, its role in goat adipogenesis remains unclear. This study investigated HOXA5’s role in regulating IMF lipid deposition in goats. Regarding differentiation, HOXA5 overexpression reduced mRNA and protein levels of differentiation genes, including CEBP/α and CEBP/β. Additionally, Oil Red O and Bodipy staining demonstrated a decrease in lipid accumulation in the HOXA5 overexpression group. Conversely, these phenotypes showed opposite trends in the HOXA5 knockdown group. Regarding proliferation, HOXA5 overexpression upregulated mRNA levels of proliferation genes, enhanced cell vitality, and increased the proportion of EdU-positive cells, while HOXA5 knockdown inhibited these phenotypes. Mechanistically, IRF7 and ABCD1 were identified as the target genes of HOXA5 by RNA-Seq and dual luciferase reporter gene assay. Functional analyses further showed that IRF7 promoted both proliferation and adipogenic differentiation, whereas ABCD1 inhibited both processes. Rescue experiments supported the involvement of IRF7 and ABCD1 in HOXA5-induced promotion of proliferation and inhibition of adipogenic differentiation. These results highlight HOXA5’s critical regulatory role in goat intramuscular adipocyte lipid deposition, offering novel insights into the underlying molecular mechanisms.