Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats.
OBJECTIVE
This study examined the effects of topiramate (TPM), a novel neurotherapeutic agent reported to reduce body weight in humans, on the components of energy balance in female Zucker rats.


METHODS
A 2 x 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotype: lean, Fa/?; obese, fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 60, 60 mg/kg).


RESULTS
The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more evident in obese than in lean rats. Whereas TPM administration did not influence the intake of digestible energy in lean rats, it induced a reduction in food intake in obese animals. In lean, but not in obese rats, apparent energy expenditure (as calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administered the vehicle. The low dose of TPM decreased fat gain (with emphasis on subcutaneous fat) without affecting protein gain, whereas the high dose of the drug induced a reduction in both fat and protein gains. The effects of TPM on muscle and fat depot weights were representative of the global effects of TPM on whole body fat and protein gains. The calculated energetic efficiency (energy gain/energy intake) was decreased in both lean and obese rats after TPM treatment. TPM dose independently reduced hyperinsulinemia of obese rats, but it did not alter insulinemia of lean animals.


CONCLUSIONS
The present results provide sound evidence for the ability of TPM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.
Centre de Recherche de l'H pital Laval, Faculté de Médecine, Université Laval, Québec, Canada.
F
F
Picard
Y
Y
Deshaies
J
J
Lalonde
P
P
Samson
D
D
Richard
D000273:Adipose Tissue; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects*; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors; D000077236:Topiramate; D015430:Weight Gain / Q000187:drug effects*
D019440:Anti-Obesity Agents; D000077236:Topiramate; D005632:Fructose