S 23521 decreases food intake and body weight gain in diet-induced obese rats.
OBJECTIVE
To investigate the effect of S 23521, a new glucagon-like peptide-1-(7-36) amide analogue, on food intake and body weight gain in obese rats, as well as on gene expression of several proteins involved in energy homeostasis.


METHODS
Lean and diet-induced obese rats were treated with either S 23521 or vehicle. S 23521 was given either intraperitoneally (10 or 100 microg/kg) or subcutaneously (100 microg/kg) for 14 and 20 days, respectively. Because the low-dose treatment did not affect food intake and body weight, the subcutaneous treatment at high dose was selected to test the effect on selected end-points.


RESULTS
Treated obese rats significantly decreased their cumulative energy intake in relation to vehicle-treated counterparts (3401 +/- 65 vs. 3898 +/- 72 kcal/kg per 20 days; p < 0.05). Moreover, their body weight gain was reduced by 110%, adiposity was reduced by 20%, and plasma triglyceride levels were reduced by 38%. The treatment also improved glucose tolerance and insulin sensitivity of obese rats. Regarding gene expression, no changes in uncoupling protein-1, uncoupling protein-3, leptin, resistin, and peroxisome proliferator-activated receptor (PPAR)-gamma were observed.


CONCLUSIONS
S 23521 is an effective glucagon-like peptide-1-(7-36) amide analogue, which induced a decrease in energy intake, body weight, and adiposity in a rat model of diet-induced obesity. In addition, the treatment also improved glucose tolerance and insulin sensitivity of obese rats. These results strongly support S 23521 as a putative molecule for the treatment of obesity.
Claret
Marc
M
Endocrinology and Nutrition Unit, Hospital Clínic de Barcelona, Villarroel 170, 08036 Barcelona, Spain.
Corominola
Helena
H
Canals
Ignasi
I
Nadal
Belén
B
Chavanieu
Alain
A
Pfeiffer
Bruno
B
Renard
Pierre
P
Gorostiaga
Carmen
C
Delagrange
Philippe
P
Grassy
Gérard
G
Gomis
Ramon
R
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
D019440:Anti-Obesity Agents; D010446:Peptide Fragments; C061970:glucagon-like peptide 1 (7-36); D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon