P>Objective Obesity and insulin resistance are associated with low adiponectin levels, although adiponectin is exclusively expressed in white adipose tissue. The mechanism beyond that paradox is not entirely clear, although insulin itself may reduce circulating adiponectin levels. However, obesity is also associated with hyperlipidaemia and the effects of free fatty acids (FFAs) and triglycerides (TG) on circulating adiponectin levels have not yet been investigated. Materials and methods We analysed the effect of an acute and euglycaemic elevation of insulin on adiponectin oligomers in 23 healthy individuals. In a subgroup including 11 healthy men, FFAs and TG were acutely elevated by infusion of heparin/lipids over 120 min. Again the effect on circulating adiponectin and its oligomers was investigated. Adiponectin was determined by ELISA, oligomers were detected by nondenaturating Western blot. Results Acute hyperinsulinaemia resulted in a significant reduction of total adiponectin to 7 center dot 74 +/- 0 center dot 98 mu g/ml (P = 0 center dot 004). High molecular weight (HMW) adiponectin did not change (0 center dot 80 +/- 0 center dot 12 to 0 center dot 81 +/- 0 center dot 14 mu g/ml; P = 0 center dot 887), whereas MMW adiponectin decreased from 4 center dot 30 +/- 0 center dot 51 to 3 center dot 78 +/- 0 center dot 48 mu g/ml (P = 0 center dot 005) and LMW adiponectin from 3 center dot 63 +/- 0 center dot 42 to 3 center dot 15 +/- 0 center dot 46 mu g/ml (P = 0 center dot 048). Interestingly, heparin/lipid infusion also reduced circulating adiponectin levels (P = 0 center dot 001), which was primarily the result of reduced MMW adiponectin (P = 0 center dot 004), whereas LMW and HMW were not significantly affected. Conclusions The presented data suggest that both, hyperinsulinaemia and hyperlipidaemia, may contribute to low adiponectin levels in states of obesity.