Mechanisms linking angiotensin to Obesity and Diabetes: role of inflammation and autophagy

• Grant number: 18/23266-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2019
• End date: July 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Joilson de Oliveira Martins
• Grantee: João Pedro Tôrres Guimarães
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/09983-3 - Role of angiotensin in obesity: inflammation and autophagy, BE.EP.DR

Abstract

Obesity is a chronic metabolic disease that may be associated with various medical disorders including, for example, Diabetes Mellitus (DM) and Hypertension (HTN). Some studies have shown common pathways linking obesity and diabetes to insulin resistance and the Renin-Angiotensin System (RAS),regulator of blood pressure. Angiotensinogen (Agt) is the main precursor of RAS, with angiotensin II (AngII) being the main bioactive hormone in this system. Agt and other RAS components are systemically detected in the circulation and locally in other tissues. Activation of Agt in adipose tissue exerts pro-inflammatory effects, often linked to dysfunctions in cellular processes, such as autophagy, a cellular pathway crucial for cellular homeostasis. Related to this proposal, our collaborator (Moustaid-Moussa) demonstrated that AngII increases inflammation in adipocytes. In Obesity, adipose tissue acquires a pro-inflammatory profile, with the production of adipokines and cytokines that promote metabolic alterations that lead to glucose intolerance and insulin resistance, as well as Diabetes. The role of immune cells or potential interactions between adipocytes and immune cells in mediating RAS effects in inflammation and autophagy has not been fully investigated. Impaired autophagy is believed to be linked with Diabetes through the development of inflammation and insulin resistance. Therefore, we hypothesized that RAS contributes to the inflammation associated with metabolic diseases through dysregulation of autophagy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GUIMARAES, JOAO PEDRO TORRES; MENIKDIWELA, KALHARA R.; RAMALHO, THERESA; QUEIROZ, LUIZ A. D.; KALUPAHANA, NISHAN S.; JANCAR, SONIA; RAMALINGAM, LATHA; MARTINS, JOILSON O.; MOUSTAID-MOUSSA, NAIMA. Effects of captopril on glucose metabolism and autophagy in liver and muscle from mice with type 1 diabetes and diet-induced obesity. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1868, n. 10, p. 13-pg., 2022-07-11. (18/50004-6, 20/03175-0, 17/11540-7, 19/09983-3, 18/23266-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GUIMARÃES, João Pedro Tôrres. Evaluation of the effect of leukotrienes and the renin angiotensin system in metabolically active tissues from mice with type 1 diabetes and obesity. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.