2013년도 생화학분자생물학회 연례국제학술대회, 2013, 02, 113─113

Chronic ethanol consumption promotes the impairment of glucose metabolism and type 2 diabetes : Role of FFA-induced ATF3

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

Abstract

Generally, it was well established that in the progression of alcoholic steatohepatitis(ASH), ceramide levels are significantly increased by alteration of sphingolipid metabolism. In particular, TNF-a is highly increased in the patients with chronic ethanol consumption, and that produced long chain free fatty acid and ceramide. Here, we examined the role of ATF3-derived ER stress on ceramide-mediated liver damages using ethanol fed mice. The level of FFA and ceramide were significantly increased in ethanol fed mice, continued with the induction of hepatic steatosis, which were determined by TNFR1-dependent pathway. Concomitantly, a novel stress-inducible tranional factor ATF3 was increased in ethanol fed mice, which were strongly attenuated by treatment of myriocin, a synthetic inhibitor of ceramide. Also, the expression of caveolin-1, CD36/FAT were increased in ethanol-treated mice. In fact, ATF3 overexpression increased ceramide-induced lipid accumulation and caveolin-1 or CD36/FAT expression, which were attenuated by ATF3 depletion. Taken together, our studies suggest that ceramide-mediated ATF3 is a regulatory pathway in dynamic regulation of lipid raft via induction of caveolin-1 and CD36/FAT, which are responsible for metabolic disorders as like in ASH models

• 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.