Adipokines and melanocortins in the hepatic manifestation of metabolic syndrome: nonalcoholic fatty liver disease

Abstract

Metabolic syndrome is associated with nonalcoholic fatty liver disease and its more aggressive form, nonalcoholic steatohepatitis. Adipokines produced by white adipose tissue possess broad physiological activity and play an important autocrine role in obesity-associated complications, including metabolic syndrome, nonalcoholic fatty liver disease and cardiovascular disease. Various adipokines may have beneficial or harmful effects. Other tissues, particularly stomach and intestine, produce active molecules that can influence the function of adipocytes and, possibly, the levels of adipokine secretion. In some cases, the production sites of these molecules remain unknown. The review focuses on our current understanding of the disease-related effects of the adipokines and the melanocortins on various peripheral tissues, and discusses some of their potential interactions with each other. Potential therapeutic applications are also considered.Expert Rev. Mol. Diagn. 7(2), 195-205 (2007) Multiple facets of metabolic syndromeMetabolic syndrome (MS) was first introduced as a clinical entity by Reaven in 1988 [1]. MS represents a cluster of risk factors commonly associated with central obesity, insulin-resistance, hypertension and elevated triglycerides, as well as decreased high-density lipoprotein cholesterol. In turn, MS is associated with an increased risk of cardiovascular disease and is a common early abnormality in the development of Type 2 diabetes. Additionally, MS plays a well-recognized role in the development of the obstructive sleep apnea, erectile dysfunction, polycystic ovary syndrome and malignant tumors. It is noteworthy that, despite tremendous clinical impact of MS, there is no clear consensus regarding the diagnostic criteria for this important nosological entity. To date, different criteria have been proposed by the WHO, by the third report of the National Cholesterol Education Program Adult Treatment Panel III (ATPIII) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, International Diabetes Federation, European Group for the Study of Insulin Resistance, and American College of Endocrinology. The problem of multiple MS definitions was recently addressed in a joint statement of The American Diabetes Association and the European Association for the Study of Diabetes [2]. The statement and other publications stress the necessity of introduction of additional criteria for MS including concentrations of the proand anti-inflammatory proteins in the serum. It is most likely that the list of the etiological factors driving the development of MS includes abnormalities in visceral adipose tissue or an altered inflammatory background that, in turn, stimulate the development of the secondary complications of MS.Recently, nonalcoholic fatty liver disease (NAFLD) and its more aggressive form, nonalcoholic steatohepatitis (NASH), have come to be regarded as the hepatic manifestation of MS. In this context, insulin resistance (IR) is 196Expert Rev. Mol. Diagn. 7(2), (2007) the key eve...