Effects of liver-specific ACSL4 (long-chain acyl-Coenzyme A synthetase 4) deletion in liver lipid metabolism

Effects of liver-specific ACSL4 (long-chain acyl-Coenzyme A synthetase 4) deletion in liver lipid metabolism Public Deposited

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Hu, Guo
- Affiliation: Gillings School of Global Public Health, Department of Nutrition

Abstract

Long-chain Acyl-CoA synthetases (ACSLs) are a family of enzymes that catalyze the thioesterification of free fatty acid to fatty acyl-CoA. One member of this family, ACSL4 has been found to be overexpressed 3-fold in patients with non-alcoholic fatty liver disease (NAFLD) though the role of ACSL4 in the pathogenesis of NAFLD is unknown. We hypothesized that the absence of ACSL4 would prevent NAFLD development. In order to test our hypothesis we developed a murine liver-specific Acsl4 knockout, fed them a high fat diet (HFD), and determined if they were protected from the development of fatty liver. Despite 20 weeks of a 45% HFD, no difference was observed in weight gain, insulin sensitivity, ACSL activity, liver triacylglycerol content, liver histology, or serum lipid metabolites between control and Acsl4 liver specific knockout animals. These results indicated that Acsl4 liver-specific KO mice were not protected from developing a fatty liver.

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