Expression of beta3-adrenoceptors with low lipolytic action in human subcutaneous white adipocytes.
Beta3-Adrenoceptors are involved in the control of catecholamine-induced lipolysis in rodent adipose tissues. The expression and function of human beta3-adrenoceptors were investigated in subcutaneous white adipocytes of young healthy women. In these cells, beta3-adrenoceptor mRNAs represent 20% of total amount of beta-adrenoceptor transcripts and less than half of beta1-adrenoceptor transcripts. Among beta3-agonists known to stimulate beta3-adrenoceptor-mediated lipolysis in rodent fat cells, only CGP12177 was able to mediate such activity in human fat cells. In in vitro lipolysis experiments and in situ microdialysis studies, CGP12177 had a 4- to 5-times lower lipolytic efficacy than isoprenaline, a nonselective beta-adrenoceptor agonist. CGP12177-induced lipolysis was antagonized in vitro by bupranolol, a beta-adrenergic antagonist potent on rodent beta3-adrenoceptors but not by nadolol, a beta1- and beta2-adrenoceptor antagonist. The in vitro blockade of isoprenaline-stimulated lipolysis by nadolol showed that the agonist acted solely via beta1- and beta2-adrenoceptors. Isoprenaline and CGP12177 were able to increase the nutritive blood flow suggesting an interaction of these molecules with receptors present in adipose tissue vessels. In conclusion, beta3-adrenoceptors are expressed in human subcutaneous white adipocytes but do not significantly contribute to isoprenaline-induced lipolysis.
Tavernier
G
G
Institut National de la Sante et de la Recherche Medicale Unite 317, Institut Louis Bugnard, Toulouse Cedex, France.
Barbe
P
P
Galitzky
J
J
Berlan
M
M
Caput
D
D
Lafontan
M
M
Langin
D
D
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008066:Lipolysis / Q000502:physiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis* / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3