Fat-specific protein 27 is a novel target gene of liver X receptor α. (15th October 2018)

• Record Type: Journal Article
• Authors: Aibara, Daisuke; Matsusue, Kimihiko; Takiguchi, Soichi; Gonzalez, Frank J.; Yamano, Shigeru
• Is Part Of: Molecular and cellular endocrinology. Volume 474(2018)
• Page Start: 48
• Page End: 56
• Publication Date: 2018-10-15
• Subjects: PPAR -- LXR -- Fatty liver -- Nuclear receptor; FSP27 fat-specific protein 27 -- CIDE cell death-inducing DNA fragmentation factor 45-like effector -- LD lipid droplet -- TG triglyceride -- PPAR peroxisome proliferator-activated receptor -- CREBH cyclic AMP-responsive element binding protein H -- LXR liver X receptor -- LXRE LXR response element -- FAS fatty acid synthase -- SCD1 stearoyl-coenzyme A desaturase 1 -- PFK2 phosphofructokinase-2 -- SREBP1c sterol regulatory element-binding protein-1c -- ChREBP carbohydrate response element-binding protein -- ACC acetyl CoA carboxylase -- GPAT glycerol-3-phosphate acyltransferase -- UTR untranslated region -- ob/ob leptin-deficient mice -- OB/OB C57BL/6J wild-type for leptin gene; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.02.006
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Fat-specific protein 27 (FSP27) is highly expressed in the fatty liver of genetically obese ob/ob mice and promotes hepatic triglyceride (TG) accumulation. The nuclear hormone receptor liver X receptor α (LXRα) also plays a critical role in the control of TG levels in the liver. The present study demonstrated transcriptional regulation of Fsp27a and Fsp27b genes by LXRα. Treatment with the LXR ligand T0901317 markedly increased Fsp27a and Fsp27b mRNAs in wild-type C57BL/6J and ob/ob mouse livers. A reporter assay indicated that two LXR-responsive elements (LXREs) are necessary for LXRα-dependent induction of Fsp27a and Fsp27b promoter activities. Furthermore, the LXRα/retinoid X receptor α complex is capable of directly binding to the two LXREs both in vitro and in vivo . These results suggest that LXRα positively regulates Fsp27a and Fsp27b expression through two functional LXREs. Fsp27a/b are novel LXR target genes in the ob/ob fatty liver. Highlights: Hepatic fat-specific protein 27 (Fsp27) promotes hepatic triglyceride accumulation. Regulation of Fsp27a and Fsp27b by the nuclear receptor liver X receptor α (LXRα) was investigated. LXRα positively regulates Fsp27a/b expression through two functional LXR-responsive elements in the 5′-upstream region. The Fsp27a/b are novel LXR target genes in the liver.