Regulation of the fatty acid synthase promoter by liver X receptor α through direct and indirect mechanisms in goat mammary epithelial cells

Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Jun LiWei Wang

Abstract

Fatty acid synthase (FASN) is a central enzyme of milk fat synthesis in the ruminant mammary gland. However, the mechanisms regulating goat FASN transcription remain elusive. The objective of this study was to investigate the mechanisms by which liver X receptor α (LXRα) regulates the FASN promoter in goat mammary epithelial cells (GMECs). In this study, T0901317 (T09), an agonist for LXRα, significantly enhanced the mRNA expression and promoter activity of FASN. Cloning of the dairy goat FASN promoter revealed the presence of one LXR response element (LXRE) and two sterol regulatory elements (SREs). Deletion or mutation of the FASN promoter LXRE reduced, but did not eliminate the transcriptional response of FASN to T09. While the LXRE and the SREs were both disrupted, basal transcription was severely reduced and there was no response to T09 treatment. This suggested that a complete response required one LXRE and two SREs. Knockdown of LXRα by siRNA did not alter the basal or T09-induced transcriptional activity of FASN. However, when sterol regulatory binding protein 1 (SREBP1) was knocked down, T09 significantly increased FASN transcription by wild-type GMECs, but had no effect on cells with LXRE-mutant promoters. The results...Continue Reading

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Citations

Aug 2, 2018·Journal of Mammary Gland Biology and Neoplasia·Xiaoyu HuYunhe Fu
Apr 10, 2019·American Journal of Physiology. Endocrinology and Metabolism·Diego Y GrinmanAdali Pecci
Jun 7, 2021·The Journal of Nutrition·Thomas SevrinMarie-Cécile Alexandre-Gouabau
Jan 23, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Manoharan BalachandiranRajaa Muthu Packirisamy

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