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World J Gastroenterol. Dec 28, 2014; 20(48): 18070-18091
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18070
Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease
Sanja Stojsavljević, Marija Gomerčić Palčić, Lucija Virović Jukić, Lea Smirčić Duvnjak, Marko Duvnjak
Sanja Stojsavljević, Marija Gomerčić Palčić, Lucija Virović Jukić, Marko Duvnjak, Department of Gastroenterology and Hepatology, Clinic of Internal medicine, Clinical hospital center “Sestre milosrdnice’’, 10000 Zagreb, Croatia
Lea Smirčić Duvnjak, University Hospital for Diabetes, Endocrinology, and Metabolic Diseases Vuk Vrhovac, 10000 Zagreb, Croatia
Author contributions: Stojsavljević S, Gomerčić Palčić M, Virović Jukić L and Duvnjak M contributed equally to this work; Duvnjak M provided the conception of the review; Stojsavljević S, Gomerčić Palčić M and Virović Jukić L participated in acquisition of data, analysis and interpretation of revised literature; Duvnjak M and Smirčić Duvnjak L critically revised the final manuscript and approved it for final submission.
Correspondence to: Marko Duvnjak, MD, PhD, Professor, Chief, Department of Gastroenterology and Hepatology, Clinic of Internal medicine, Clinical hospital center “Sestre milosrdnice’’, Vinogradska cesta 29, 10000 Zagreb, Croatia. marko.duvnjak1@gmail.com
Telephone: +385-98-9838930 Fax: +385-1-3787448
Received: June 24, 2014
Revised: October 21, 2014
Accepted: November 18, 2014
Published online: December 28, 2014
Processing time: 196 Days and 5.4 Hours
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Keywords: Nonalcoholic fatty liver disease; Cytokines; Adipokines; Adiponectin; Leptin; Tumor necrosis factor-α; Interleukin-6; Interleukin-1; Interleukin-18; Ghrelin

Core tip: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is still not fully elucidated. We explored the role of the following adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD: adiponectin, leptin, ghrelin, resistin and visfatin among adipokines, and tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 among proinflammatory cytokines. Although a definite conclusion is complex, from analyzed data we could conclude that adiponectin, des-acyl ghrelin and leptin are adipokines that decrease, while TNF-α and IL-6 are cytokines that enhance insulin resistance and subsequently NAFLD. Acting on these premises, new therapeutic possibilities emerge; however, much work remains to be done.