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001-es BibID:BIBFORM065903
Első szerző:Kristóf Endre (általános orvos)
Cím:Clozapine modifies the differentiation program of human adipocytes inducing browning / Endre Kristóf, Quang-Minh Doan-Xuan, Anitta Kinga Sárvári, Ágnes Klusóczki, Pamela Fischer-Posovszky, Martin Wabitsch, Zsolt Bacso, Péter Bai, Zoltán Balajthy, László Fésüs
Dátum:2016
Megjegyzések:Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not 6 other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser-scanning cytometry showed that up to 40% of the differentiating single primary and SGBS adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly up-regulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested if browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the up-regulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine induced beige cells displayed increased basal and oligomycin inhibited (proton leak) oxygen consumption but these cells showed a lower response to cAMP stimulus as compared to control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for treatment of SGA-induced weight gain.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
adipocita
beige
clozapine
lézer-pásztázó citometria
elhízás
szerotonin
termogenezis
Megjelenés:Translational Psychiatry. - 6 : 11 (2016), p. 1-12. -
További szerzők:Doan-Xuan, Quang-Minh (1986-) (biofizikus) Sárvári Anitta Kinga (1984-) (biológus) Klusóczki Ágnes (1991-) (biotechnológus) Fischer-Posovszky Pamela Wabitsch, Martin Bacsó Zsolt (1963-) (biofizikus) Bai Péter (1976-) (biokémikus) Balajthy Zoltán (1957-) (biokémikus, sejtbiológus) Fésüs László (1947-) (orvos biokémikus)
Pályázati támogatás:TÁMOP-4.2.4.A/2-11/1-2012-0001
TÁMOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0023
TÁMOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0025
TÁMOP
TRANSCOM IAPP 251506
FP7
MTA-DE
MTA
Apoptózis és Genomika Kutatócsoport
K108308
OTKA
NK105046
OTKA
GINOP-2.3.2-15-2016-00006
GINOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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