Special reports and reviewNonalcoholic Fatty Liver Disease: Cytokine-Adipokine Interplay and Regulation of Insulin Resistance
Section snippets
Cytokines in NAFLD
Identification of the mechanisms that cause and mediate obesity-related fatty liver disease are awaited and progress in the past few years has been substantial.6, 7 Cytokines are critically involved in the physiology of a healthy liver and in the pathophysiology of many acute and chronic liver diseases. These mediators are released by almost all cell types in the liver and play a fundamental role in liver function and regeneration. Cytokines are key mediators of hepatic inflammation, liver cell
Adiponectin, the Key TNFα-Neutralizing Adipocytokine, and Its Role in Inflammation and NAFLD
Adipose tissue and its metabolic products recently have gained great interest. Various products of the fat tissue have been characterized including not only cytokines such as TNFα or IL-6, but also the so-called adipo(cyto)kines including leptin, adiponectin, and visfatin.8 Adiponectin, the predominant protein synthesized by adipocytes, circulates in rather high concentrations and shows a wide spectrum of biological activities.
Adiponectin is secreted predominantly from adipose tissue and shares
Hepatic IR and Underlying Mechanisms
The first link between obesity, increase in the expression of a proinflammatory cytokine, namely TNFα, and insulin action came from a study more than 13 years ago.95 These findings led to the concept of inflammation in obesity and showed that adipocytes express TNFα. In these studies, expression of this cytokine in obese animals (fa/fa rat and ob/ob mouse) has been increased and shown to regulate insulin action.95 Further evidence supporting a key role for TNFα in IR came from studies published
Conclusions
NAFLD has emerged as a major cause of abnormal liver function tests worldwide and is considered an integral part of the metabolic syndrome. Accumulating insights should help clinicians to consider this diagnosis even when patients present without other clinical features of the metabolic syndrome, thereby allowing early identification of this syndrome. Cytokines and adipokines seem to play a major role at various stages of NAFLDs and improvement of understanding in the past few years has clearly
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Supported by the Christian Doppler Society and a grant from the Austrian Science Foundation (P17447), National Institutes of Health USA (DK52539 and DK64360), and the American Diabetes Association.