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.


METHODS
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.


CONCLUSIONS
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.
Ricci
M R
MR
Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick 08901-8525, USA.
Fried
S K
SK
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D015152:Blotting, Northern; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005260:Female; D005470:Fluorometry; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D005990:Glycerol / Q000032:analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D020738:Leptin; D008297:Male; D009767:Obesity, Morbid / Q000235:genetics / Q000503:physiopathology*; D009852:Omentum / Q000503:physiopathology; D009924:Organ Culture Techniques; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry; D011863:Radioimmunoassay
D000318:Adrenergic beta-Agonists; D017931:DNA Primers; D005938:Glucocorticoids; D007328:Insulin; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D007545:Isoproterenol; D005990:Glycerol