Adiponectin is an adipocyte-derived protein suggested to be involved in energy homeostasis and in lipid and glucose metabolism. Little is known regarding the consequence of acute changes in energy balance on adiponectin mRNA expression in human adipose tissue. Using a real-time RT-PCR assay, we investigated the effects of 2-d very low calorie diet (VLCD) and subsequent refeeding on adiponectin mRNA expression in sc adipose tissue of morbidly obese women. Basal adiponectin mRNA abundance of the obese women showed a wide distribution (2.6-14.3 mRNA/18S rRNA; coefficient of variation, 51.2%) and was significantly lower than that of lean controls (P < 0.001). In the obese group, the VLCD caused a 33% rise (P < 0.01) in the average level of mRNA, whereas refeeding caused a 32.8% fall (P < 0.05). In contrast, the change in leptin mRNA expression with either VLCD or refeeding was not statistically significant. The obese subjects who showed an acute adiponectin mRNA response to the changes in energy intake had a higher basal level of adiponectin mRNA (P = 0.02) and a borderline-significantly lower body mass index compared with the subjects who showed no or weak adiponectin mRNA response. Insulin sensitivity of the responder subgroup significantly increased by 89% (P = 0.008) after the VLCD, whereas insulin sensitivity of the nonresponder subgroup only increased by 24% (P = 1.56). This study indicates that adiponectin mRNA in sc adipose tissue can acutely respond to short-term energy changes in some obese subjects. Both the levels of adiposity and insulin sensitivity may contribute to the variation in adiponectin gene expression in response to acute energy changes.