Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

World J Gastroenterol. 2014 Dec 28;20(48):18070-91. doi: 10.3748/wjg.v20.i48.18070.


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

Publication types

  • Review

MeSH terms

  • Adipokines / metabolism*
  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism*
  • Animals
  • Cytokines / metabolism*
  • Humans
  • Inflammation Mediators / metabolism*
  • Liver / immunology
  • Liver / metabolism*
  • Liver / pathology
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Signal Transduction


  • Adipokines
  • Cytokines
  • Inflammation Mediators