2013년 한국알코올과학회 춘계학술대회 ""음주와 만성질환"", 2013, 02, 100─100

The regulatory mechanisms involved in in ethanol-induced hepatic steatosis

KeonJae Park, Ji Yeon Kim, Dae Yeon Lee, Gyu Hee Kim, Eun Ae Jung, Won-Ho Kim

Abstract

In the onset and progression of ASH and NASH, ceramide is significantly increased by alterations of sphingolipid. However, the regulatory mechanisms by which ceramide drives hepatic steatosis remain poorly understood. Here, we examined the role of ATF3 on ceramide-mediated liver steatosis in ethanol-fed mice or HFD-fed rats. Hepatic steatosis increased in both models are correlated with the increase of ceramide levels in their serum or liver tissues, accompanied with the expression of FAS and SREBP1, which was determined by TNF-α production and TNFR1-dependent pathway. Concomitantly, a stress-inducible ATF3 was significantly increased in these models and it plays as a potent regulator for de novo ceramide synthesis and ceramide-mediated lipid accumulation. Also, ATF3 directly regulates FAS and SREBP1 expression, thereby increases ceramide-mediated lipogenesis and inhibits insulin receptor signaling, which were abolished by ATF3 siRNA. Taken together, our studies suggest that ceramide-mediated ATF3 is a critical regulatory pathway in dynamic regulation of lipid accumulation.

• 본 연구는 질병관리본부 연구개발과제(과제번호 2011-NG64001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2011-NG64001-00) by Research of Korea Centers for Disease Control and Prevention.