Background/Aims Since a novel polypeptide named adiponectin was shown to prevent the development of steatosis and steatohepatitis in animal models, we studied whether it was also possible in a clinical situation. Methods Associations between serum adiponectin levels and serum transaminase activities were studied in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV or HCV induced liver diseases. Results Various markers of metabolic diseases including levels of body mass index (BMI), serum triglyceride, total cholesterol, and insulin resistance assessed by the homeostasis model were significantly higher in subjects with increased transaminase activities when compared to those with normal activities. Single regression analyses demonstrated that the logarithmic serum adiponectin level was inversely correlated with the levels of logarithmic serum AST(r=-0.229,P< 0.0001), ALT (r=-0.305, P< 0.0001), and γ GTP(r=-0.278, P< 0.0001). Even in multiple regression analyses in which subjects age and levels of BMI, serum triglyceride, total cholesterol, and insulin resistance were adjusted, the inverse correlations were significant (P=0.0426, 0.0332, and 0.0011,respectively). Conclusions Hypoadiponectinemia may worsen liver diseases associated with metabolic diseases in clinical cases. In addition to aggravation of insulin resistance and hyperlipidemia,some hypoadiponectinemia specific mechanisms may stand behind the association. Background / Aims Since a novel polypeptide named adiponectin was shown to prevent the development of steatosis and steatohepatitis in animal models, we studied whether it was also possible in a clinical situation. Methods Associations between serum adiponectin levels and serum transaminase activities were studied in 791 Japanese males who were not heavy drinkers, and had no autoimmune or HBV or HCV induced liver diseases. Results Various markers of metabolic diseases including levels of body mass index (BMI), serum triglyceride, total cholesterol, and insulin resistance assessed by the homeostasis model were significantly higher in subjects with increased transaminase activities when compared to those with normal activities. Single regression analyzes demonstrated that the logarithmic serum adiponectin level was inversely correlated with the levels of logarithmic serum AST (r = -0.229, P <0.0001), ALT (r = -0.305, P <0.0001), and γ GTP (r = -0.278, P <0.0001). Even in multiple regression analys es in which subjects age age and levels of BMI, serum triglyceride, total cholesterol, and insulin resistance were adjusted, the inverse correlations were significant (P = 0.0426, 0.0332, and 0.0011, respectively). Conclusions Hypoadiponectinemia may worsen liver diseases associated with metabolic diseases in clinical cases. In addition to aggravation of insulin resistance and hyperlipidemia, some hypoadiponectinemia specific mechanisms may stand behind the association.