DEXAMETHASONE, OB GENE, AND LEPTIN IN HUMANS - EFFECT OF EXOGENOUS HYPERINSULINEMIA

This study was undertaken to investigate temporal association between dexamethasone administration, OB gene expression, and leptin response in humans in the presence and absence of exogenous hyperinsulinemia. S ix healthy males (age 24.5 +/- 1.0 yr, body mass index 26.4 +/- 1.0, b ody fat 16.2 +/- 1.8%) received 10 mg oral dexamethasone in five divid ed doses twice (protocols A and B) 1-2 weeks apart beginning at 0800 h on day 1 and ending at 0700 h on day 2. The dexamethasone administrat ion was combined with two subcutaneous abdominal fat biopsies performe d at 0800 h before and after dexamethasone administration (protocol A) , or 4-h isoglycemic hyperinsulinemic (300 mU/m(2) BSA/min, protocol B ) clamp carried out between 0900 and 1300 h on day 2. OB gene expressi on (protocol A) did not change. In both protocols on day 2, the 0800 h leptin levels nearly doubled (P < 0.001), whereas 1300 h levels nearl y quadrupled (P < 0.001). The elevation in leptin persisted until 0800 h of day 3 (24 h after last dexamethasone dose) with its subsequent r apid normalization. The short-term isoglycemic hyperinsulinemia (proto col B) had no additional effect on the postdexamethasone leptin respon se. We summarize that: 1) 24-h administration of dexamethasone has a m arked stimulatory effect on circulating leptin levels but not on OB ge ne expression in the subcutaneous abdominal fat. 2) The effect is sust ained for the next 24 h. 3) Short-term hyperinsulinemia has no additio nal effect. We conclude that dexamethasone is a powerful stimulator of leptin production in vivo through a mechanism that appears to be inde pendent of OB gene transcription in the human subcutaneous abdominal f at.