Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not.
Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12-week diets of chow or chow plus candy. The latter were randomized for 12 further weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert to chow-only diet. Energy expenditure was measured, and oral glucose tolerance tests (OGTTs) were performed. Body composition was determined by dual-energy X-ray absorptiometry scanning, and pancreatic beta-cell mass was determined by histology. Candy feeding increased weight, fat mass, and feeding-associated energy expenditure. Liraglutide or reversal to chow diet fully reversed weight and fat gains. Liraglutide was associated with decreased calorie intake and shifted food preference (increased chow/decreased candy consumption). Despite weight loss, liraglutide-treated rats did not decrease energy expenditure compared with candy-fed controls. Vildagliptin affected neither weight, food intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly suggested that both drugs increased insulin sensitivity. Liraglutide and vildagliptin inhibited obesity-associated increases in beta-cell mass. This was associated with weight and fat mass normalization with liraglutide, but not vildagliptin, where the ratio of beta-cell to body mass was low.
Raun
Kirsten
K
Department of Pharmacology Research 3, Novo Nordisk A/S, Maaloev, Denmark. kira@novonordisk.com
von Voss
Pia
P
Gotfredsen
Carsten F
CF
Golozoubova
Valeria
V
Rolin
Bidda
B
Knudsen
Lotte Bjerre
LB
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D002182:Candy; D002149:Energy Intake / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000069450:Liraglutide; D009570:Nitriles; D009765:Obesity; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D011759:Pyrrolidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077597:Vildagliptin
D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane