Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Aug 14, 2010; 16(30): 3731-3742
Published online Aug 14, 2010. doi: 10.3748/wjg.v16.i30.3731
AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability
Yoon Mee Yang, Chang Yeob Han, Yoon Jun Kim, Sang Geon Kim
Yoon Mee Yang, Chang Yeob Han, Sang Geon Kim, Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea
Yoon Jun Kim, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea
Author contributions: Yang YM and Han CY were responsible for the review of the literature and initial preparation of the paper; Kim YJ added information on clinical perspectives; Kim SG proposed the concept and prepared the final version of the manuscript.
Supported by The National Research Foundation of Korea Grant, Funded by the Korea Government (MEST), No. 2010-0001706, South Korea
Correspondence to: Sang Geon Kim, PhD, Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy, Seoul National University, Gwanak-ro 599, Gwanak-gu, Seoul 151-742, South Korea. sgk@snu.ac.kr
Telephone: +82-2-8807840 Fax: +82-2-8721795
Received: February 16, 2010
Revised: March 25, 2010
Accepted: April 2, 2010
Published online: August 14, 2010

The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function.

Keywords: Adenosine monophosphate-activated protein kinase, Cell survival, Energy metabolism, Fatty liver, Insulin resistance, Glycogen synthase kinase 3β, p70 ribosomal S6 kinase-1