Isoproterenol Decreases Leptin Expression in Adipose Tissue of Obese Humans

OBJECTIVE: We investigated the effects of the non-selective beta-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 microM). 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 approximately 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 beta-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.