The shared physiopathologic derangements linking nonalcoholic fatty liver disease (NAFLD) with the metabolic syndrome (MetS), along with the biological basis of treatment, will be discussed in this review. The role of macrophages in the 'adipositis of the obese individual mirrors that of Kupffer cells in NAFLD. The gut plays a major role in the pathogenesis of NAFLD by contributing to the development of insulin resistance and inflammation. Mitochondrial dysfunction is the cellular basis for impaired energy homeostasis in adipose, muscle and liver tissues. NAFLD is an essential component of the MetS. However, ethnicity, gender, genetic and hormonal influxes - via body fat distribution - modulate the propensity to develop NAFLD, accounting for the finding that few NAFLD patients are seemingly spared from developing the MetS. Future studies should aim at evaluating the role of hypathalamic inflammation in MetS in humans. Furthermore, moderate calorie restriction and weight loss provide prompt metabolic benefit in NAFLD, with indications suggesting that the Mediterranean-type diet has the potential for curing the MetS and NAFLD. The controversial role of alcohol and the molecular mechanism of actions exerted by physical training on NAFLD are discussed in this article. Additionally, specific molecular/cellular targets for innovative treatment strategies based on NAFLD physiology are also reviewed. © 2010 Expert Reviews Ltd.
Clinical physiology of NAFLD: A critical overview of pathogenesis and treatment / Lonardo, A.; Caldwell, S. H.; Loria, Paola. - In: EXPERT REVIEW OF ENDOCRINOLOGY & METABOLISM. - ISSN 1744-6651. - ELETTRONICO. - 5:(2010), pp. 403-423. [10.1586/eem.10.5]