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Obesity and insulin resistance: iNOS effect on intestinal microbiota and endoplasmic reticulum stress in liver and adipose tissue of mice

Grant number: 16/07122-2
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2016
Effective date (End): April 01, 2019
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Mario Jose Abdalla Saad
Grantee:Tamires Marques Zanotto
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):17/10179-9 - Evaluation of intestinal microbiota and the mechanism of S-nitrosation in iNOS KO mice treated with high-fat diet, BE.EP.DD


Obesity is a consequence of factors such as over nutrition and sedentary lifestyle, which leads to weight gain and several metabolic disorders, especially Insulin Resistance (IR) and Type II Diabetes (DM2). Several intracellular mechanisms are associated with the IR emergence, among them, is the iNOS enzyme, which activity is induced by pro-inflammatory cytokines in obesity. Many studies have demonstrated this enzyme overexpression in obese mice peripheral tissues, and its inhibition reverses fasting hyperglycemia and decreases hyperinsulinemia in these mice. Recently, the gut microbiota was also identified as a potential trigger of IR during obesity, with an increase in iNOS expression capable of changes in this tissue. Other relevant aspect is this enzyme potential involvement on the occurrence of Endoplasmic Reticulum (ER) Stress, since there is an increased expression and/or activity in these situations. However, the mechanisms by which inactivation of iNOS protects against ER stress was not completely elucidated. In this sense, the present study aimed to investigate the direct and indirect role of iNOS on endoplasmic reticulum stress ocurrence in liver and adipose tissue of mice treated with High Fat Diet (HFD). The iNOS direct involvement on the ER stress will be investigated by s-nitrosation evaluation of UPR key proteins (ATF6± and PERK), and the indirect involvement by intestinal microbiota evaluation of the profile and circulating bacterial metabolites (LPS, short chain fatty acids etc.), as well as these metabolites effect on ER stress in liver and adipose tissue of these mice. (AU)

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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)
ZANOTTO, TAMIRES M.; QUARESMA, PAULA G. F.; GUADAGNINI, DIOZE; WEISSMANN, LAIS; SANTOS, ANDRESSA C.; VECINA, JULIANA F.; CALISTO, KELLY; SANTOS, ANDREY; PRADA, PATRCIA O.; SAAD, MARIO J. A.. Blocking iNOS and endoplasmic reticulum stress synergistically improves insulin resistance in mice. MOLECULAR METABOLISM, v. 6, n. 2, . (12/15009-0, 13/07607-8, 16/07122-2)
BAGAROLLI, RENATA A.; TOBAR, NATALIA; OLIVEIRA, ALEXANDRE G.; ARAUJO, TIAGO G.; CARVALHO, BRUNO M.; ROCHA, GUILHERME Z.; VECINA, JULIANA F.; CALISTO, KELLY; GUADAGNINI, DIOZE; PRADA, PATRICIA O.; et al. Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 50, p. 16-25, . (12/15009-0, 16/07122-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ZANOTTO, Tamires Marques. Blocking iNOS and endoplasmic reticulum stress sinergistically improves insulin sensitivity. 2019. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.

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