The role of PDE4 inhibition on hypothalamic neuroinflammation and leptin resistance

• Grant number: 19/20602-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2019
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Hellen Veida Paraguassu da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

It is well known that obesity is related to chronic low-grade inflammation and an increase in pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF). The inhibition of Phosphodiesterase 4 (PDE4) can strongly inhibit the release of TNF and reduce inflammation after LPS challenge. Additionally, it was shown that PDE4 -/- mouse is resistant to diet-induced obesity. This study aims to evaluate the effect of rolipram, a phosphodiesterase 4 inhibitor, on diet-induced obesity. Male C57Bl6 mice will be fed with either chow or high-fat diet (HFD; 60% fat) for 10 weeks and in the 8 weeks, they will receive a vehicle (VEH) or rolipram (ROL) subcutaneous injections. During the experimental period, food intake and body weight will be monitored and at the end of the study inguinal, retroperitoneal and brown fat pads will be collected for analysis. (AU)