Effect of the ACAA1 Gene on Preadipocyte Differentiation in Sheep

Abstract

Acetyl-CoA acyltransferase 1 (<i>ACAA1</i>) functions as a key regulator of fatty acid β-oxidation in peroxisomes by catalyzing the cleavage of 3-ketoacyl-CoA to acetyl-CoA and acyl-CoA, which participate in the extension and degradation of fatty acids. Thus, <i>ACAA1</i> is an important regulator of lipid metabolism and plays an essential role in fatty acid oxidation and lipid metabolism. Our previous study findings revealed that <i>ACAA1</i> is closely associated with the peroxisome proliferator-activated receptor (<i>PPAR</i>) signaling and fatty acid metabolism pathways, which are involved in fat deposition in sheep, leading to our hypothesis that <i>ACAA1</i> may be involved in fat deposition by regulating lipid metabolism. However, the associated molecular mechanism remains unclear. In the present study, to assess the potential function of <i>ACAA1</i> in sheep preadipocyte differentiation, we knocked down and overexpressed <i>ACAA1</i> in sheep preadipocytes and evaluated the pattern of <i>ACAA1</i> gene expression during preadipocyte differentiation by qRT-PCR. <i>ACAA1</i> was significantly expressed in the early stage of adipocyte differentiation, and then its expression decreased. <i>ACAA1</i> deficiency increased lipid accumulation and the triglyceride content and promoted sheep preadipocyte differentiation, whereas <i>ACAA1</i> overexpression inhibited adipogenesis and decreased lipid accumulation and the triglyceride content. Simultaneously, we demonstrated that <i>ACAA1</i> deficiency upregulated the expressions of the adipogenic marker genes <i>PPAR</i>γ and <i>C/EBP</i>α in sheep preadipocytes, but <i>ACAA1</i> overexpression inhibited the expressions of these markers, indicating that <i>ACAA1</i> affects lipid metabolism by regulating adipogenic marker genes. Our results may promote a better understanding of the regulation of adipogenesis by <i>ACAA1</i>.