Circulating soluble CD14 monocyte receptor is associated with increased alanine aminotransferase.

Abstract

Recent studies have suggested that abnormal hepatocellular function is associated with obesity, insulin resistance, and type 2 diabetes (1)(2)(3). Nonancoholic fatty liver disease (NAFLD) is the preferred term to describe a spectrum of liver damage, ranging from steatosis to steatohepatitis, liver fibrosis, and cirrhosis, that can be found in insulin-resistant (obese and type 2 diabetic) and hyperlipidemic patients (4). Insulin sensitivity and liver function exhibit a bidirectional relationship: a normally functioning liver determines, in part, the normal body response to insulin, whereas abnormal insulin sensitivity causes liver damage (5)(6). The insulin-resistant state is characterized by a failure to suppress hepatic glucose production and glycogenolysis (5), usually accompanied by fat accumulation in hepatocytes as a result of increased hepatic uptake and synthesis of triglycerides. The latter is known to impair liver function and, consequently, to worsen insulin resistance (5)(6). Aminotransferases are considered indicators of hepatocellular health. Alanine aminotransferase (ALT) is found primarily in the liver, whereas aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (γGT) are also found in other tissues. NAFLD is characterized by mild-to-moderate increases in ALT and AST (7). Recent prospective studies have shown that increased ALT and γGT are predictors of the development of type 2 diabetes (1)(2). CD14, a 55-kDa glycoprotein, is a multifunctional receptor constitutively expressed in considerable amounts on the surface of mature monocytes, macrophages, and neutrophils (8). CD14 has specificity for lipopolysaccharide (LPS) and other bacteria-wall-derived components (9). LPS signaling triggers a cascade that leads to cytokine production and shedding of the extracellular domain of CD14 (sCD14) (10)(11)(12)(13). The buffering of LPS is crucial not only during acute inflammatory and infectious processes; in healthy humans, triglyceride-rich lipoproteins contain detectable amounts of endogenous LPS that are presumably scavenged in …