EVALUATION OF THE EFFECTS OF PHOSPHODIESTERASE 4 INHIBITOR ON LEPTIN ACTION IN LIPOLYSIS IN DIET-INDUCED OBESITY

• Grant number: 22/12488-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2022
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Luiza Mendonça Duarte
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/18071-5 - Hydroelectrolytic and energy homeostasis: from cellular metabolism to endocrine systems in different phases of development, AP.TEM

Abstract

Obesity became a public health issue as it is characterized by chronic systemic inflammation, affecting regions such as the hypothalamus and causing the development of other health complications, such as cardiovascular diseases, insulin and leptin resistance. Therefore, there is a clear interest in studying the mechanisms that are activated on inflammation and how to attenuate these effects to restrain obesity progress. One of these mechanisms is the inhibition of phosphodiesterase 4 (PDE4), an enzyme associated to inflammation because of its regulatory activity on cyclic adenosine monophosphate (cAMP), participating in cAMP hydrolysis to 5'AMP. When PDE4 is inhibited, 5'AMP concentration is reduced, promoting the reduction of inflammation by activating anti-inflammatory signaling pathways. Thus, this study aims to evaluate the effects of PDE4 inhibition with rolipram on diet-induced obesity. For this purpose, male mice C57bl-6 will receive a regular diet (CHOW) or a high fat diet (HFD) for a 10-week period, and, after the eighth week, they will be treated with vehicle (VEH) or rolipram (ROL). In the last two days of the last week, animals will receive either vehicle or leptin in order to test leptin sensitivity. At the end of the experiment, food intake, body weight and fat pads weight will be evaluated. The tissues collected will be used to verify the expression of phosphorylated HSL enzyme, perilipin and catecholamines, in addition to genes related to inflammation and thermogenesis.