Role of angiotensin in obesity: inflammation and autophagy

• Grant number: 19/09983-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): December 01, 2019
• Effective date (End): November 30, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Joilson de Oliveira Martins
• Grantee: João Pedro Tôrres Guimarães
• Supervisor: Naima Moustaid-Moussa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Texas Tech University (TTU), United States
• Associated to the scholarship: 18/23266-0 - Mechanisms linking angiotensin to Obesity and Diabetes: role of inflammation and autophagy, BP.DR

Abstract

Obesity is a chronic metabolic disease that may be associated with physiological disorders, such as diabetes mellitus (DM) and hypertension. Studies have shown common pathways linking obesity to insulin resistance and the renin-angiotensin system (RAS). Angiotensinogen (Agt) is the main precursor of RAS. Activation of Agt is often linked to dysfunctions in cellular processes, such as autophagy. In obesity, the pro-inflammatory profile in adipose tissue leads to the production of adipokines and cytokines that promote glucose intolerance and insulin resistance. Leukotriene B4 (LTB4) plays a central role in the establishment of insulin resistance and development of low grade inflammation in animal models. In adipose tissue of HFD induced T2D mice, monocyte recruitment, macrophage polarization into the M1 profile, proinflammatory cytokine production and insulin resistance have been shown to be dependent on LTB4 production. In liver and muscle LTB4 promotes inflammation and insulin resistance. We intend to investigate the involvement of leukotrienes in RAS in mice with obesity, with specific emphasis on the role of inflammation, autophagy and signaling of the insulin receptor in metabolically active organs/tissues. Understanding the molecular mechanisms involved in these diseases can bring a direct benefit to the patient, improving their quality of life, as well as reducing the public expenses resulting from the complications of these metabolic syndromes. (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)