Study of cellular senescence in rodents subjected to Obesity

• Grant number: 20/06397-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2020
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Silvana Auxiliadora Bordin da Silva
• Grantee: Caio Jordão Teixeira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
• Associated scholarship(s): 22/02829-1 - The role of AGEs in activation of PRRs by gut microbiota from mice fed with a high-fat high-sucrose diet, BE.EP.PD

Abstract

The increasing prevalence of Obesity has assumed characteristics of a pandemic that is directly associated with the risk of developing Hypertension, cardiovascular disease, Dyslipidemia, Type 2 Diabetes Mellitus (T2DM) and Non-Alcoholic Fatty Liver Disease (NAFLD). Such comorbidities make Obesity contribute to reduced life expectancy. It is known that excess of adipose tissue is accompanied by a subclinical inflammatory state, leading to increased expression of various proinflammatory cytokines and infiltration of immune mononuclear cells into pivotal tissues for energy metabolism. In addition to promoting the accumulation of Advanced Glycation End products (AGEs) in these tissues, recent studies show that Obesity intensifies the cell senescence phenotype. In this context, although a dietary education can normalize caloric intake, there is no total reversal of body weight, inflammation of adipose tissue and morphological changes in the endocrine pancreas in mice with a history of Obesity, which makes evident the existence of a metabolic memory caused by the obese phenotype. In this way, the present study aims to establish whether the increase in AGEs in animals with a transient history of Obesity induced by obesogenic diet triggers the pathway of pancreatic islet senescence in order to result in persistent changes in their phenotype. To achieve this purpose, we will study several morphofunctional parameters as well as the signaling pathway of senescence in islets of mice subjected to a history of Obesity. In addition to this exploratory strategy, we will study whether inhibition of AGEs synthesis during Obesity plays a role in this metabolic memory. Another protocol proposed to evaluate the role of AGEs will be to investigate whether transient exposure to methylglyoxal simulates the impacts caused by a transient history of Obesity on the endocrine pancreas. In vitro protocols with MIN6 cells will also be performed to investigate a possible irreversible action of AGEs on activation of senescence pathways in pancreatic beta-cells. (AU)

Scientific publications

(7)

(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)

DE SOUZA, DAILSON NOGUEIRA; TEIXEIRA, CAIO JORDAO; VERONESI, VANESSA BARBOSA; MURATA, GILSON MASAHIRO; SANTOS-SILVA, JUNIA CAROLINA; HECHT, FERNANDA BALLERINI; VICENTE, JULIA MODESTO; BORDIN, SILVANA; ANHE, GABRIEL FORATO. Dexamethasone programs lower fatty acid absorption and reduced PPAR-gamma and fat/CD36 expression in the jejunum of the adult rat offspring. Life Sciences, v. 265, JAN 15 2021. (13/07607-8, 20/06397-3, 19/03196-0, 16/13138-9, 15/23285-6)

ASSALIN, HELOISA B.; GABRIEL DE ALMEIDA, KELLY CRISTIANE; GUADAGNINI, DIOZE; SANTOS, ANDREY; TEIXEIRA, CAIO J.; BORDIN, SILVANA; ROCHA, GUILHERME Z.; SAAD, MARIO J. A.. Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 22, p. 18-pg., 2022-11-01. (19/03196-0, 14/50907-5, 20/06397-3)

HECHT, FERNANDA BALLERINI; TEIXEIRA, CAIO JORDAO; DE SOUZA, DAILSON NOGUEIRA; NUNES MESQUITA, FILIPHE DE PAULA; DO VAL ROSO, RYANA ELYZABETH; SODRE, FRHANCIELLY SHIRLEY; VERONESI, VANESSA BARBOSA; DA ROCHA, DEBORAH FABIANA; DANTAS DE MENEZES, YAN GUIDA; PIOLI, MARIANA RODRIGUES; et al. Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats. BIOMEDICINE & PHARMACOTHERAPY, v. 144, DEC 2021. (19/03196-0, 13/07607-8, 20/09717-9, 16/13138-9, 20/06397-3)

VERONESI, VANESSA BARBOSA; PIOLI, MARIANA RODRIGUES; DE SOUZA, DAILSON NOGUEIRA; TEIXEIRA, CAIO JORDAO; MURATA, GILSON MASAHIRO; SANTOS-SILVA, JUNIA CAROLINA; HECHT, FERNANDA BALLERINI; VICENTE, JULIA MODESTO; BORDIN, SILVANA; ANHE, GABRIEL FORATO. Agomelatine reduces circulating triacylglycerides and hepatic steatosis in fructose-treated rats. BIOMEDICINE & PHARMACOTHERAPY, v. 141, SEP 2021. (16/13138-9, 13/07607-8, 15/23285-6, 20/06397-3, 17/20742-2, 19/03196-0)

ALMEIDA, LORENA DE SOUZA; TEIXEIRA, CAIO JORDAO; CAMPOS, CAROLINA VIEIRA; CASALOTI, LAIS GUADALUPE; SODRE, FRHANCIELLY SHIRLEY; CAPETINI, VINICIUS COOPER; AMARAL, ANDRESSA GODOY; PAYOLLA, TANYARA BALIANI; PANTALEAO, LUCAS CARMINATTI; ANHE, GABRIEL FORATO; et al. Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats. METABOLITES, v. 12, n. 10, p. 15-pg., 2022-10-01. (13/07607-8, 20/13940-5, 19/03196-0, 20/06397-3)

CAMPOS, CAROLINA VIEIRA; TEIXEIRA, CAIO JORDAO; PAYOLLA, TANYARA BALIANI; CRISMA, AMANDA RABELLO; MURATA, GILSON MASAHIRO; AMARAL, ANDRESSA GODOY; PANTALEAO, LUCAS CARMINATTI; SODRE, FRHANCIELLY SHIRLEY; ONARI, MARIANA MAYUMI; ALMEIDA, LORENA DE SOUZA; et al. Changes in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers. LIVERS, v. 1, n. 4, p. 20-pg., 2021-12-01. (13/07607-8, 16/23008-5, 20/09717-9, 20/06397-3, 19/03196-0, 14/02977-4, 16/22605-0)

SELLAMI, EYA; EVANGELISTA-SILVA, PAULO HENRIQUE; TEIXEIRA, CAIO JORDAO; DIOP, KHOUDIA; MITCHELL, PATRICIA; ANHE, FERNANDO FORATO. High fructose rewires gut glucose sensing via glucagon-like peptide 2 to impair metabolic regulation in mice. MOLECULAR METABOLISM, v. 93, p. 13-pg., 2025-01-29. (20/06397-3, 22/14545-8, 20/12201-4, 22/02829-1)