Abstract
Nonalcoholic fatty liver disease (NAFLD), the major reason for abnormal liver function in the Western world, is associated with obesity and diabetes and is characterized by insulin resistance (IR). IR is regulated by mediators released from cells of the immune system or adipocytes and proinflammatory cytokines such as tumor necrosis factor-α (TNFα). The importance of TNFα in human and animal fatty liver diseases, both caused by genetic manipulation and overnutrition, has been shown convincingly. Furthermore, neutralization of TNFα activity improves IR and fatty liver disease in animals. Adiponectin is a potent TNFα-neutralizing and anti-inflammatory adipokine and in vitro and experimental animal studies have proven the importance of this mediator in counteracting inflammation and IR. Anti-inflammatory effects of adiponectin are exerted both by suppressing TNFα synthesis and by induction of anti-inflammatory cytokines such as interleukin-10 or interleukin-1–receptor antagonist. Therefore, the balance between various mediators, either derived from the immune system or adipose tissue, appears to play an important role in hepatic and systemic insulin action and in the development of fatty liver disease.
Highlights
There is compelling evidence that (1) enhanced liver tumor necrosis factor (TNF)␣ expression is observed in animal models and human beings with nonalcoholic steatohepatitis (NASH)/Nonalcoholic fatty liver disease (NAFLD), (2) this cytokine, released by many cells in the body including various cell types in liver and adipocytes, is crucially involved in the pathogenesis of insulin resistance (IR), and (3) neutralization of TNF␣, at least in experimental animal models, improves IR, hepatic steatosis, and liver inflammation
Adiponectin, the predominant protein synthesized by adipocytes, circulates in rather high concentrations and shows a wide spectrum of biological activities
Adiponectin exists in the circulation as a full-length and a putative proteolytic cleavage fragment consisting of the globular C-terminal domain, which might have enhanced activity within high-order complexes
Summary
Tilg, Herbert, and Gökhan S. Hotamisligil. 2006. “Nonalcoholic Fatty Liver Disease: Cytokine-Adipokine Interplay and Regulation of Insulin Resistance.” Gastroenterology 131 (3): 934–45. https:// doi.org/10.1053/j.gastro.2006.05.054. This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-ofuse#LAA
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