This study by Bajnok et al. investigated the relationship between adiponectin and paraoxonase 1 (PON1), which is an HDL-associated anti-atherosclerotic factor that plays a role in the antioxidant and other pleiotropic functions of HDL cholesterol. They examined the potential relationship of PON1 activity with markers of the metabolic syndrome in three age- and sex-matched groups: 25 non-diabetic overweight/obese subjects (body mass index (BMI) between 28 and 39.9 kg/m2), 25 non-diabetic subjects with morbid obesity (BMI?40 kg/m2), and 24 healthy, normal-weight controls. Among the three subgroups, the normal-weight control group was characterized by higher PON1 activity as well as higher adiponectin concentrations compared to the two other groups. Results of this study also demonstrated that PON1 activity correlated positively with HDL cholesterol and adiponectin concentrations and correlated negatively with several markers of the metabolic syndrome such as BMI, waist circumference, systolic blood pressure, HbA1c and insulin levels, insulin resistance index (based on homeostasis model assessment), as well as lipid peroxidation indices (i.e., thiobarbituric acid reactive substances). Multiple regression analyses also revealed that the positive association between plasma adiponectin levels and PON1 activity was independent of HDL cholesterol levels. Thus, the authors suggested that adiponectin may enhance the hepatic production of PON1. These findings indicate that adiponectin is an independent predictor of PON1 activity, which may partly explain why adiponectin has anti-atherosclerotic effects.