Summary Elevated circulating alanine aminotransferase (ALT) and ␥ -glutamyltransferase ( ␥ -GTP) activities, and the accumulation of fat, particularly visceral fat, in healthy and preclinical subjects reportedly increase the risk for metabolic diseases such as diabetes. In the present study, we examined the associations between these hepatic enzymes and the total visceral and subcutaneous fat area, and for both regions of fat independently, in healthy and preclinical middle-aged Japanese men. We conducted a cross-sectional study of men who participated in health check-ups in Japan. We removed participants, who were diagnosed with metabolic diseases at the time of the health check-up. Three hundred fifteen subjects aged 40-64 y (mean Ϯ SD, 50.5 Ϯ 6.9 y) were selected. We compared associations between the total visceral and subcutaneous fat area, and for both regions independently, with various clinical parameters, including hepatic enzyme markers, using Spearman's rank correlation coefficient analysis and multiple linear regression analysis. The total visceral and subcutaneous fat area and both regions independently were positively associated with body mass index, systolic and diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, ALT and ␥ -GTP. ALT and ␥ -GTP activities were the strongest explanatory variables for increased visceral fat area, independent of the subcutaneous fat area. In contrast, these hepatic enzymes were not explanatory variables for increased subcutaneous fat area. The results of the present study show that the accumulation of visceral fat is positively associated with ALT and ␥ -GTP activities independently of subcutaneous fat area in healthy and preclinical Japanese men. Key Words ALT, ␥ -GTP, visceral fat, Japanese men, healthy and preclinical subjects Abnormalities in metabolic parameters such as hyperglycemia and lipid levels promote the development of diabetes, metabolic syndrome and related complications such as cardiovascular disease, hypertension and inflammation in peripheral tissues ( 1-3 ). Thus, it is necessary to identify biomarkers that can predict the development of these diseases. Recent studies have demonstrated that the circulating activity of ␥ -glutamyltransferase ( ␥ -GTP), a hepatic enzyme that is considered to represent liver injury and hepatic disorders, is a marker for inflammation and oxidative stress in healthy and preclinical subjects. This is because the circulating ␥ -GTP activity is closely associated with oxidative stress markers (e.g., lipid peroxides) and the inflammatory marker C-reactive protein (CRP) in healthy subjects in Western countries and in Japan, and because ␥ -GTP itself contributes to the production of reactive oxygen species (ROS) ( 4-8 ). In addition, the circulating activity of alanine aminotransferase (ALT), another hepatic enzyme marker for liver injury, is associated with liver insulin resistance in subjects in Western countries and in Japan ( 9-11 ). It has bee...