ICEECE2012 Poster Presentations Neuroendocrinology (83 abstracts)
Topiramate treatment improves hypothalamic insulin and leptin signaling and action and reduces obesity in mice
A. Caricilli 1 , Penteado 1 , F. Mittestainer 1 , L. Abreu 1 , P. Quaresma 1 , A. Santos 1 , D. Guadagnini 1 , D. Razolli 1 , L. Velloso 1 , M. Saad 1 & P. Prada 1,
1State University of Campinas, Campinas, Brazil; 2State University of Campinas, Limeira, Brazil.
Topiramate (TPM) is an anticonvulsant drug used for the treatment of epilepsy and prophylaxis of migraine. Weight loss is a side effect frequently reported in patients and animal models treated with TPM. Some studies showed that TPM may decrease energy storage, and thus increase energy expenditure and thermogenesis. However, the mechanisms by which TPM reduces body weight are not completely understood. Anorexigenic hormones such as insulin and leptin regulate the activity of distinct neuron populations that control energy balance via IR/PI3K/Akt/Foxo1 pathway or OBR/JAK2/STAT3 pathway respectively. However, whether TPM alters hypothalamic insulin or leptin sensitivity is not known. Thus, in the present study, we investigated whether TPM treatment alters energy balance by altering insulin and leptin action/signaling in the hypothalamus from control and diet-induced obesity (DIO) mice. Swiss mice fed with standard chow or high-fat diet were orally treated with TPM (100 mg/kg/day) during 7 days. TPM treatment led to decreased body weight gain in DIO mice, but not in control mice, with increased oxygen consumption, fat oxidation and UCP-1 expression in brown adipose tissue. Moreover, TPM treatment followed by intracerebroventricular insulin and leptin infusion increased hypothalamic insulin and leptin signaling and action in obese mice, respectively, which led to decreased food intake and increased energy expenditure, with higher levels of CRH, TRH and CART, and reduced levels of NPY, MCH and orexin mRNA expression. However, when mice were pair-fed, no significant differences were observed concerning body weight gain and hypothalamic insulin and leptin signaling in TPM-treated mice compared with non-treated animals. In conclusion, the reduced food intake and increased energy expenditure induced by TPM are associated with hypothalamic insulin and leptin regulation and may reduce obesity in mice on high-fat feeding, presenting an alternative therapy for the treatment of obesity.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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