Adipocytokine levels in nonalcoholic fatty liver disease
Authors: Teoman Dogru, Cemal Nuri Ercin, Serkan Tapan, Murat Kantarcioglu, Muammer Kara, Sait Bagci
Journal: Hepatology (2009)

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity increasingly recognized as a major health burden in developed countries. It includes a spectrum of liver damage ranging from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and, rarely, progression to cirrhosis. Recent studies have emphasized the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines, and mitochondrial dysfunction in the development and progression of NAFLD. Furthermore, accumulating evidence supports an association between NAFLD and metabolic syndrome. Hence, obesity, dyslipidemia, hypertension, and hyperglycemia are strongly associated with NAFLD. Although the data are mainly epidemiological, the pathogenesis of NAFLD and metabolic syndrome seem to have common pathophysiological mechanisms, with a focus on insulin resistance as a key factor.1 In a recent issue of HEPATOLOGY, Milner et al.2 reported the association of some newly described adipocytokines with histopathological findings, insulin sensitivity, and dyslipidemia in subjects with NAFLD (NASH and SS) and healthy controls. This study is important because it provides scientific information on this clinically relevant condition. However, we think that some points should be discussed. First, as shown in Table 1 in the article,2 most of the participants (especially in the NASH and SS groups) were obese. In addition, there were significant differences in the body mass index and in the levels of glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between the groups. It is well known that circulating adipokines and measures of insulin sensitivity are easily affected by these metabolic factors.3-5 Second, NAFLD is strongly associated with obesity, hypertension, and glucose tolerance abnormalities.6 It has been reported that all these metabolic problems are risk factors for type 2 diabetes mellitus and also prediabetes, that is, impaired fasting glucose and/or impaired glucose tolerance. Although it is stated in the article that some of the patients were diabetic at baseline, there is no information regarding the glucose tolerance status of the other subjects. In light of these clear data, we think that some of the study participants may still have had overt glucose dysregulation or type 2 diabetes mellitus without implementation of the glucose tolerance test. This issue is important because NAFLD is associated with prediabetes and blood adipokine and insulin levels are altered in subjects with disordered glucose metabolism.7, 8 Finally, the diabetic subjects were taking different classes of antidiabetic medications in the study. It has been reported that circulating adipokines and measures of insulin sensitivity are easily affected by these drugs.9, 10 We conclude that, before certain interpretations are made, the presence of major confounders for adipocytokines and insulin resistance raises some questions about the data presented. In such a case, statistical correlations may also be misleading. It would be appreciated if the authors could present some more data adjusted for major metabolic confounders. This could provide readers clearer information with respect to the link between adiposity, adipokines, insulin sensitivity, and NAFLD. Teoman Dogru*, Cemal Nuri Ercin*, Serkan Tapan , Murat Kantarcioglu*, Muammer Kara*, Sait Bagci*, * Department of Gastroenterology, Gulhane School of Medicine, Ankara, Turkey, Department of Biochemistry, Gulhane School of Medicine, Ankara, Turkey.