Work

Acetyl-CoA acyltransferase 2 as a metabolic modulator: Unraveling its impact on hepatic lipid dynamics in chicken embryos

Year: 2025

Type: article

Abstract: Despite the established role of acetyl-CoA acyltransferase 2 (ACAA2) in hepatic lipid homeostasis in mammals, its function in regulating hepatic lipid metabolism during the embryonic stage of chickens remains unexplored. This study aimed to explore the regulatory role of ACAA2 in hepatic lipid metabolism and investigate its molecular mechanisms in chicken embryos. A recombinant ACAA2-shRNA plasmid was successfully constructed for targeted suppression of ACAA2 expression. Knockdown of ACAA2 significantly increased triglyceride content, promoted lipid droplet accumulation, and upregulated lipogenesis-related gene expression in chicken embryos. The knockdown of ACAA2 significantly suppressed both mRNA and protein expression of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyl transferase 1 (CPT1), while conversely upregulating sterol regulatory element binding protein-1c (SREBP-1c) mRNA and protein expression. Notably, these metabolic alterations caused by ACAA2 knockdown were markedly reversed by the activation of PPARα in primary chicken embryonic hepatocytes, suggesting functional crosstalk between the ACAA2 and PPARα signaling pathways. These results indicate that fat accumulation action of the knockdown of ACAA2 was due to enhancing SREBP-1c expression and reducing PPARα expression. In present study, ACAA2 was identified as a critical modulator of embryonic lipid metabolism, offering a target for interventions to reduce embryonic mortality or metabolic diseases in poultry.

Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

DOI: 10.1016/j.bbalip.2025.159674