The effect of peripheral and central inhibition of phosphodiesterase 4 on diet-induced inflammation

• Grant number: 22/09687-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2022
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Francisco José Albuquerque de Paula
• Grantee: Hellen Veida Paraguassu da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 23/14038-1 - Participation of adrenergic modulation in the effects of PDE4 inhibition on fatty liver in obese mice, BE.EP.DD

Abstract

Phosphodiesterase 4 (PDE4) is an enzyme that hydrolyzes cAMP (cyclic adenosine monophosphate), reducing intracellular cAMP concentrations. It was recently shown that PDE4 knockout mouse is resistant to diet-induced obesity. Additionally, preliminary data from this study demonstrated that PDE4 inhibition with rolipram reduces food intake and adiposity, which is associated with an energy expenditure increase. However, the exact mechanisms whereby PDE4 inhibition exerts its metabolic effects remain to be elucidated. Here, we propose investigating the impact of central and peripheral inhibition of PDE4 in diet-induced obesity. C57bl-6 mice will be fed a high-fat diet for 12 weeks, after 10 weeks of HFD treatment they will be treated with rolipram, YM-976 or vehicle for 2 weeks. Animals will then be decapitated and tissue will be used for gene expression assessment in the hypothalamus, white and brown adipose tissue. Moreover, we will also evaluate the effect of PDE4 inhibition in body composition and insulin sensitivity. (AU)