Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects.
OBJECTIVE
The action of noradrenaline on human mesenteric, omental and subcutaneous adipocytes was compared. We also determined whether regional differences in the noradrenaline-effect were linked to variations in adrenoceptor subtype function.


METHODS
The lipolytic effects of different concentrations of noradrenaline (beta 1-, beta 2-, beta 3- and alpha 2-adrenoceptor agonist), isoprenaline (beta 1-, beta 2- and beta 3-adrenoceptor agonist) and selective beta 1-, beta 2- and beta 3-adrenoceptor agonists (dobutamine, terbutaline and CGP 12177, respectively) were studied in adipocytes isolated from the three adipose tissue regions in the same subject. In addition, the effect of the alpha 2-adrenoceptor antagonist, yohimbine, was studied on noradrenaline-induced glycerol release.


METHODS
Thirteen otherwise healthy obese subjects (nine females, four males).


RESULTS
The noradrenaline-induced lipolytic response did not differ between omental and mesenteric adipocytes but was 50% higher than in subcutaneous adipocytes (P < 0.05). Furthermore, noradrenaline sensitivity and intrinsic activity (in relation to isoprenaline) were higher in the two visceral fat cells than in the subcutaneous fat cells. The intrinsic activity of noradrenaline increased close to that of isoprenaline when yohimbine was added to the incubation system. Isoprenaline sensitivity was five times higher in the two visceral fat cells than in the subcutaneous fat cells. For CGP 12177, sensitivity and intrinsic activity did not differ between mesenteric and omental adipocytes, but was higher in these two regions when compared to subcutaneous adipocytes. For dobutamine and terbutaline no significant regional differences were found.


CONCLUSIONS
beta 3-adrenoceptor action is enhanced and alpha 2-adrenoceptor action is decreased in both mesenteric and omental adipocytes as compared to subcutaneous adipocytes. However, the two visceral fat depots show no difference in adrenoceptor function. The difference in beta 3- and alpha 2-adrenoceptor function might explain why noradrenaline induced lipolysis is increased in the two visceral fat depots, as compared to the subcutaneous fat depot.
Van Harmelen
V
V
Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Lönnqvist
F
F
Thörne
A
A
Wennlund
A
A
Large
V
V
Reynisdottir
S
S
Arner
P
P
D017667:Adipocytes / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008643:Mesentery; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*; D009852:Omentum; D011412:Propanolamines / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D015016:Yohimbine; D004280:Dobutamine; D007545:Isoproterenol; D013726:Terbutaline; C033394:CGP 12177; D009638:Norepinephrine