In vivo effects of CGP-12177 on the expression of leptin and uncoupling protein genes in mouse brown and white adipose tissues.
OBJECTIVE
To assess the effect of chronic treatment with CGP-12177 a beta3-adrenergic receptor (AR) agonist with beta2/beta1-AR antagonist action, on the expression of the leptin gene and of genes coding for uncoupling proteins (ucp1, ucp2 and ucp3) in brown and white adipose tissues.


METHODS
NMRI mice received a daily subcutaneous injection of CGP-12177 at a dose of 0.05, 0.2, 0.5 or 1 mg/kg for 15 days. The specific levels of the mRNAs of interest were analysed in interscapular brown adipose tissue (BAT) and in two white adipose tissue (WAT) depots, inguinal (IWAT) and epididymal (EWAT).


RESULTS
No changes in food intake or body weight were detected at any dose of CGP-12177. In the two WAT depots, the treatment led to enhanced expression of ucp1 and ucp3, but not of ucp2. In BAT, low doses (0.05 and 0.2 mg/kg) led to a decreased expression of the three ucp genes, whereas a slight stimulatory effect on the three ucp genes was elicited with a high dose (1 mg/kg). Treated animals displayed increased expression of leptin in BAT and, to a lesser extent, in IWAT, but not in EWAT.


CONCLUSIONS
The results reveal that simultaneous stimulation of the expression of certain ucp genes and the leptin gene can be achieved, and suggest that adrenergic regulation of the leptin gene and of genes of the ucp family in adipose tissues is the result of complex interactions between the different beta-AR pathways.
Oliver
P
P
Departament de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain.
Picó
C
C
Martínez
N
N
Bonet
M L
ML
Palou
A
A
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D007279:Injections, Subcutaneous; D007473:Ion Channels; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins; D011412:Propanolamines / Q000008:administration & dosage*; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D017931:DNA Primers; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011412:Propanolamines; D011506:Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C033394:CGP 12177