Adiponectin, a newly discovered adipose-tissue-specific protein, is thought to be involved in the regulation of insulin action. The aim of the present study was to determine whether adiponectin contributes to the improvement in insulin sensitivity during very-low-calorie diet (VLCD). Biopsies of sc abdominal adipose tissue and blood sampling for analysis of plasma adiponectin and related hormones and metabolites were performed before and at the end of a 4-wk VLCD in 33 nonmorbidly obese women (body mass index, 34.4 +/- 4.1 kg/m(2)). VLCD produced a decrease in weight (7.1 +/- 0.4 kg) and in insulin and leptin levels and led to an improvement in insulin sensitivity. Adiponectin gene expression and plasma levels were not modified during calorie restriction. Before VLCD, we found negative correlations between plasma adiponectin and variables related to the metabolic syndrome. Adiponectin mRNA levels showed a negative correlation with lipoprotein a plasma values. The correlations observed before VLCD were not found after VLCD. The data suggest that adiponectin is related to the protection against the metabolic syndrome but is not involved in the regulation of VLCD-induced improvement of insulin sensitivity.