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Central role of GLP-1 agonists (liraglutide) and antiepileptic (topiramate) in treatment of high-fat diet-induced Obesity

Grant number: 18/19942-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2019
Effective date (End): July 31, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Licio Augusto Velloso
Grantee:Rodrigo Stellzer Gaspar
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:15/50278-0 - Anti-obesity effects of nutrients by hypothalamic FFA1 and FFA4 activation, AP.TEM


Obesity is one of the major public health problems in the world. The rapid increase in its prevalence raises with it a number of comorbidities and complications. Effective long-term treatments are challenging and often require multiple approaches, such as behavioral, lifestyle changes, eating habits, increased physical activity and drug treatments. Recent studies have shown that both GLP-1 agonists (liraglutide) and an antiepileptic agent (topiramate) lead to weight loss in obese patients and are approved for marketing in several countries. Because they are drugs with action in the central nervous system, it is believed that, at least in part, they regulate the function of anorexigenic neurons of the hypothalamus, particularly POMC. Objective: To evaluate the central effect of liraglutide and topiramate in the treatment of high-fat diet-induced obesity with a primary focus on their individual ability to regulate gene expression in POMC neurons. Materials and methods: C57BL/6J male mice, on high-fat diet for 8 weeks, will receive either vehicle; liraglutide or topiramate via intraperitoneal (IP) for 3 days. Will be evaluated: food intake; adipose mass; glucose and insulin tolerance tests; respirometry; body temperature and RNA sequencing. Values will be expressed as mean ± standard deviation and will be analyzed by T-test (2 groups) or one-way ANOVA, with Bonferroni post-hoc. The level of significance will be p <0.05. Prospects: Differentially expressed genes may aid in the creation of drugs aimed at the treatment of Obesity in the long term, elucidating mediators responsible for reducing food intake and inflammation induced by high-fat diet. (AU)