AUTHOR=Wang Yanli , Li Xin , Cao Yang , Xiao Cheng , Liu Yu , Jin Haiguo , Cao Yang 

TITLE=Effect of the ACAA1 Gene on Preadipocyte Differentiation in Sheep

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.649140

DOI=10.3389/fgene.2021.649140

ISSN=1664-8021

ABSTRACT=<p>Acetyl-CoA acyltransferase 1 (<italic>ACAA1</italic>) 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, <italic>ACAA1</italic> 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 <italic>ACAA1</italic> is closely associated with the peroxisome proliferator-activated receptor (<italic>PPAR</italic>) signaling and fatty acid metabolism pathways, which are involved in fat deposition in sheep, leading to our hypothesis that <italic>ACAA1</italic> 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 <italic>ACAA1</italic> in sheep preadipocyte differentiation, we knocked down and overexpressed <italic>ACAA1</italic> in sheep preadipocytes and evaluated the pattern of <italic>ACAA1</italic> gene expression during preadipocyte differentiation by qRT-PCR. <italic>ACAA1</italic> was significantly expressed in the early stage of adipocyte differentiation, and then its expression decreased. <italic>ACAA1</italic> deficiency increased lipid accumulation and the triglyceride content and promoted sheep preadipocyte differentiation, whereas <italic>ACAA1</italic> overexpression inhibited adipogenesis and decreased lipid accumulation and the triglyceride content. Simultaneously, we demonstrated that <italic>ACAA1</italic> deficiency upregulated the expressions of the adipogenic marker genes <italic>PPAR</italic>γ and <italic>C/EBP</italic>α in sheep preadipocytes, but <italic>ACAA1</italic> overexpression inhibited the expressions of these markers, indicating that <italic>ACAA1</italic> affects lipid metabolism by regulating adipogenic marker genes. Our results may promote a better understanding of the regulation of adipogenesis by <italic>ACAA1</italic>.</p>