Liver X receptor α mediates hepatic triglyceride accumulation through upregulation of G0/G1 Switch Gene 2 expression.

Autor:	Heckmann BL; Department of Biochemistry and Molecular Biology.; HEALth Program, Mayo Clinic in Arizona, Scottsdale, Arizona, USA.; Mayo Graduate School, Rochester, Minnesota, USA., Zhang X; Department of Biochemistry and Molecular Biology.; HEALth Program, Mayo Clinic in Arizona, Scottsdale, Arizona, USA., Saarinen AM; Department of Biochemistry and Molecular Biology.; HEALth Program, Mayo Clinic in Arizona, Scottsdale, Arizona, USA., Schoiswohl G; Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Kershaw EE; Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Zechner R; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Liu J; Department of Biochemistry and Molecular Biology.; HEALth Program, Mayo Clinic in Arizona, Scottsdale, Arizona, USA.; Division of Endocrinology, Mayo Clinic in Arizona, Scottsdale, Arizona, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2017 Feb 23; Vol. 2 (4), pp. e88735. Date of Electronic Publication: 2017 Feb 23.
DOI:	10.1172/jci.insight.88735
Abstrakt:	Liver X receptors (LXRs) are transcription factors essential for cholesterol homeostasis and lipogenesis. LXRα has been implicated in regulating hepatic triglyceride (TG) accumulation upon both influx of adipose-derived fatty acids (FAs) during fasting and stimulation of de novo FA synthesis by chemical agonism of LXR. However, whether or not a convergent mechanism is employed to drive deposition of FAs from these 2 different sources in TGs is undetermined. Here, we report that the G0/G1 Switch Gene 2 (G0S2), a selective inhibitor of intracellular TG hydrolysis/lipolysis, is a direct target gene of LXRα. Transcriptional activation is conferred by LXRα binding to a direct repeat 4 (DR4) motif in the G0S2 promoter. While LXRα -/- mice exhibited decreased hepatic G0S2 expression, adenoviral expression of G0S2 was sufficient to restore fasting-induced TG storage and glycogen depletion in the liver of these mice. In response to LXR agonist T0901317, G0S2 ablation prevented hepatic steatosis and hypertriglyceridemia without affecting the beneficial effects on HDL. Thus, the LXRα-G0S2 axis plays a distinct role in regulating hepatic TG during both fasting and pharmacological activation of LXR. Competing Interests: Conflict of interest: The authors have declared that no conflict of interest exists.
Databáze:	MEDLINE
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