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Mechanisms linking angiotensins to obesity and Diabetes: role of inflammation, endoplasmic reticulum stress and autophagy

Grant number: 18/50004-6
Support Opportunities:Regular Research Grants
Start date: August 01, 2018
End date: July 31, 2020
Field of knowledge:Health Sciences - Pharmacy
Agreement: Texas Tech University
Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
Principal Investigator:Joilson de Oliveira Martins
Grantee:Joilson de Oliveira Martins
Principal researcher abroad: Naima Moustaid-Moussa
Institution abroad: Texas Tech University (TTU), United States
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:17/11540-7 - Investigating the role of insulin in the presence of allergic pulmonary inflammation in diabetic and healthy mice, AP.R

Abstract

Obesity is a complex disease that increases mortality and associated comorbities such as diabetes and cardiovascular diseases. One of the critical pathways involved in obesity is the Renin Angiotensin System (RAS) which is classically known to regulate blood pressure and fluid balance is also expressed in adipose tissue. RAS contributes to inflammation in obesity and diabetes and is often linked to dysfunctions in cellular processes. These include the endoplasmic reticulum (ER) stress and autophagy, which are not well understood. We hypothesize that RAS contributes to metabolic diseases-associated inflammation through dysregulated ER stress and autophagy in adipocytes and immune cells (macrophages). We will test this hypothesis using mice overexpressing RAS specifically in the adipose tisssie to determine changes in these cellular processes. Additionally, we will investigate the mechanisms mediating these effects using adipocytes and cultured macrophages. Further, since adipose tissue is also composed of immune cells, it is critical to investigate the interactions between adipocytes and macrophages to better understand how they affect diabetes and obesity. Our proposal will help identify new potential targets for reducing RAS-induced obesity and related metabolic diseases. Importantly the foundation for the proposed research is based on strong established and complementary expertise and published work by the TTU (obesity/adipose tissue and USP (immunology partnering teams. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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., . (18/50004-6, 20/03175-0, 17/11540-7, 19/09983-3, 18/23266-0)