Inhibitions of FASN suppress triglyceride synthesis via the control of malonyl-CoA in goat mammary epithelial cells

Abstract

Fatty acid synthase (FASN) is the key enzyme for de novo fatty acid synthesis from acetyl-CoA and malonyl-CoA. All the steps involved in fatty acid synthesis by FASN have been clearly defined in monogastrics and ruminants. However, there are no data on the mechanism of how FASN affects triglyceride synthesis. Inhibition of FASN in goat mammary epithelial cells by C75, a synthetic inhibitor of FASN activity, and shRNA markedly suppressed the accumulation of triglyceride in goat mammary epithelial cells. Meanwhile, C75 treatment significantly reduced the relative content of monounsaturated fatty acids (C16:1 and C18:1). Corresponding to the suppression of lipid accumulation, both of C75 and shRNA also decreased the mRNA expression of GPAM, AGPAT6 and DGAT2, all of which are related to triglyceride synthesis. The fact that treatment of malonyl-CoA decreased the expression of these genes is consistent with the results of shRNA treatment. Furthermore, the supplement of malonyl-CoA enhanced the suppression on GPAM, AGPAT6, LPIN1, DGAT1 and DGAT2. The results underscore the role of malonyl-CoA in inhibition of FASN in regulating triglyceride synthesis in goat mammary epithelial cells.