Expression of FASN regulated by NR1H2 or NR1H3

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Reaction [omitted]
Homo sapiens
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The fatty acid synthase (FAS or FASN) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. FASN is a central enzyme in de novo lipogenesis. Expression of FASN gene is regulated by the sterol regulatory element-binding transcription factor 1 (SREBP1 or SREBF1) pathway. The FASN promoter was found to be a target for a direct regulation by liver X receptor α (LXRα) and LXRβ (also known as NR1H3 and NR1H2, respectively) (Joseph SB et al. 2002). Agonists of NR1H2 or NR1H3 induced expression of FASN in various mammalian cells including human monocyte-like THP-1 and hepatocellular carcinoma HepG2 cell lines (Joseph SB et al. 2002; Matsukuma KE et al. 2007). In vivo studies showed that mice carrying a targeted disruption in the NR1H3 (LXRα) gene were deficient in expression of FAS, SCD1, and SREBF1 (Peet DJ et al. 1998). The administration of T0901317, a synthetic agonist of NR1H2, NR1H3 upregulated FASN gene expression in both diabetic db/db and nondiabetic C57BLKS mice (Chisholm JW et al. 2003). It also resulted in a more severe hypertriacylglycerolemia and hepatic triacylglycerol accumulation in the db/db diabetic than observed in nondiabetic mice (Chisholm JW et al. 2003). Consistent with in vivo studies, treating HepG2 cells with T0901317 induced lipid accumulation and the expression of lipogenic genes such as FAS, SCD1, and SREBP1c (Li M et al. 2016).

Literature References
PubMed ID Title Journal Year
17684114 The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor

Herzog, B, Hallberg, M, Seth, A, Woods, A, White, R, Parker, MG

Mol. Endocrinol. 2007
11790787 Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors

Joseph, SB, Laffitte, BA, Patel, PH, Watson, MA, Matsukuma, KE, Walczak, R, Collins, JL, Osborne, TF, Tontonoz, P

J. Biol. Chem. 2002
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