Retinol Binding Protein-4 Circulating Levels Were Higher in Nonalcoholic Fatty Liver Disease Vs. Histologically Normal Liver From Morbidly Obese Women

IntroductIonNonalcoholic fatty liver disease (NAFLD) has frequently been associated with obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and insulin resistance, which are the main features of metabolic syndrome (1,2).NAFLD is an increasingly recognized condition that has become the most common liver disorder in the developed world (1).NAFLD causes a wide spectrum of liver damage, ranging from simple steatosis (SS) to cirrhosis.In most cases, SS does not progress to a more severe disease, but ~20-30% of patients have histological signs of fibrosis and necroinflammation, indicating a presence of nonalcoholic steatohepatitis (NASH) (3).The pathogenesis of NAFLD is poorly understood and much of the current opinion remains hypothetical.Obesity is considered an important risk factor, though not all patients with NAFLD are obese (4).In obesity, an altered secretion of proteins takes place in the adipose tissue, the so-called adipokines, which have wide-ranging endocrine and paracrine effects on general metabolism (5).These adipokines are considered important determinants of obesity-related disorders such as insulin resistance, inflammation, and dyslipidemia (6).Consequently, there is growing evidence that adipokines are one of the causal links between obesity and NAFLD (7).A recently identified adipokine is the retinol binding protein-4 (RBP4), the specific carrier protein of retinol (vitamin A) in the blood.Although the major tissue site of RBP4 synthesis in the body is the liver, other sites of synthesis have been reported such as adipose tissues, kidney, and brain (8-10).It has been put forward that adipose tissue in humans, as occurs in mice, has the second highest level of RBP4 expression (8).Circulating RBP4 levels have been associated with estimations of adiposity and insulin resistance (11-13).Interestingly, we and others have reported a downregulation of RBP4 messenger RNA (mRNA) in subcutaneous adipose tissue (SAT)