Isoproterenol Decreases Leptin Expression in Adipose Tissue of Obese Humans

RICCI, MATTHEW R. AND SUSAN K. FRIED. Isoproterenol decreases leptin expression in adipose tissue of obese humans. Obes Res . Objective : We investigated the effects of the non‐selective β‐adrenergic agonist, isoproterenol (Iso), on leptin expression in human adipose tissue. Research Methods and Procedures : Subcutaneous (SQ) and omental adipose (OM) tissue taken during surgery from 12 morbidly obese subjects (10 women and 2 men) were cultured for up to 24 hours with insulin (7 nM) and/or dexamethasone (25 nM), a synthetic glucocorticoid, in the presence or absence of isoproterenol (10 μM). Adipose tissue was also acutely incubated for 3 hours in media alone with or without isoproterenol. Leptin secretion and leptin mRNA abundance were measured. Results : Iso acutely decreased leptin release by −30% (vs. no hormone controls) in fragments of OM and SQ adipose tissue. In 24‐hour culture, addition of Iso (in the presence of insulin) resulted in lower leptin accumulation in the medium (−20–30%) and leptin mRNA levels (−40–50%) from both tissue depots. Culture with insulin and dexamethasone increased leptin expression vs. insulin alone. Addition of Iso with insulin and dexamethasone decreased media leptin (−40–60%) and leptin mRNA levels were lower (−65%) in Iso‐treated adipose tissue from both depots after 24 hours. Iso effects were not detectable after 5 hours of culture. Discussion : We conclude that stimulation of β‐adrenergic receptors may modulate leptin expression in human adipose tissue by two mechanisms: an acute effect on leptin release and a longer‐term antagonism of stimulatory effects of insulin and dexamethasone on leptin mRNA expression. These mechanisms may contribute to the decline in serum leptin that occurs during fasting.