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World J Gastroenterol. Jun 21, 2014; 20(23): 7325-7338
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7325
Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease: A controversial issue
Wilhelmus J Kwanten, Wim Martinet, Peter P Michielsen, Sven M Francque
Wilhelmus J Kwanten, Peter P Michielsen, Sven M Francque, Laboratory of Experimental Medicine and Paediatrics, University of Antwerp, 2000 Antwerp, Province of Antwerp, Belgium
Wim Martinet, Laboratory of Physiopharmacology, University of Antwerp, 2000 Antwerp, Province of Antwerp, Belgium
Peter P Michielsen, Sven M Francque, Department of Gastroenterology Hepatology, Antwerp University Hospital, B-2650 Edegem, Province of Antwerp, Belgium
Author contributions: Kwanten WJ contributed to literature research and writing of the paper; Martinet W contributed to critical review for intellectual content; Michielsen PP contributed to critical review for intellectual content; Francque SM contributed to writing of the paper, critical review for intellectual content, coordination.
Supported by Fund for Scientific Research (FWO) - Flanders (11J9513N, G007412N, G044312N, 1802514N), to Kwanten WJ, Martinet W and Francque SM
Correspondence to: Sven M Francque, MD, PhD, Department of Gastroenterology Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Province of Antwerp, Belgium. sven.francque@uza.be
Telephone: +32-3-8214572 Fax: +32-3-8214478
Received: October 12, 2013
Revised: December 24, 2013
Accepted: January 8, 2014
Published online: June 21, 2014
Processing time: 251 Days and 14.5 Hours
Abstract

Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients. The potential role of autophagy in disease is increasingly recognised and investigated in the last decade. Nowadays it is commonly accepted that autophagy plays a role in the hepatic lipid metabolism. Hence, dysfunction of autophagy may be an underlying cause of non-alcoholic fatty liver disease. However, controversy of the exact role of autophagy in the lipid metabolism exists: some publications report a lipolytic function of autophagy, whereas others claim a lipogenic function. This review aims to give an update of the present knowledge on autophagy in the hepatic lipid metabolism, hepatic insulin resistance, steatohepatitis and hepatic fibrogenesis.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic fatty liver disease; Steatohepatitis; Non-alcoholic steatohepatitis; Autophagy; Lipophagy; Lipid metabolism

Core tip: Autophagy is a mechanism involved in cellular homeostasis. In this review the current knowledge on the role of autophagy in non-alcoholic fatty liver disease (NAFLD) is summarised, with emphasis on the current controversy on the lipolytic vs lipogenic function in hepatic lipid metabolism. Furthermore the role of autophagy in the pathophysiology of insulin resistance, hepatocellular injury and fibrogenesis is reviewed to better understand its importance in NAFLD.