Advanced glycated albumin and insulin resistance in rats: focus on periepididimal adipose tissue and N-acetylcysteine actions

• Grant number: 12/18724-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2012
• Effective date (End): March 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marisa Passarelli
• Grantee: Karolline Santana da Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives, AP.TEM

Abstract

Advanced glycation end products (AGE) contribute to the pathogenesis of chronic complications in diabetes mellitus (DM). In macrophages, AGE enhance the uptake of cholesterol-enriched lipoproteins and diminish cholesterol efflux mediated by HDL. Besides AGE induce oxidative stress and inflammation in these cells which may contribute to the progression of atherosclerosis from the arterial wall and peripheral point of view considering that macrophage infiltration in different organs and tissues modulates the local inflammatory response and abnormal lipid metabolism. The objective of this project is to analyze the effect of chronic administration of AGE-albumin in rats associated or not with N-acetylcystein (NAC) treatment in the inflammatory status of peritoneal and adipose tissue macrophages. Our hypothesis is that AGE can increase the inflammatory status in macrophages independently of hyperglycemia and that NAC could prevent/revert this effect which was not evaluated in an in vivo model so far. Male Wistar rats will be randomically assigned to four experimental groups receiving: 1) control (C) albumin ; 2) C-albumin + NAC; 3) AGE-albumin and 4) AGE-albumin + NAC. Animals will receive C or AGE-albumin (20 mg/kg/dia) by daily intraperitoneal injections and NAC in the water, for 90 days. It will be determined the histological profile of periepididimal adipose tissue and M1 and M2 macrophage differentiation as well as the mRNA expression of inflammatory citokynes, RAGE, AGE-R1 and CD-36. In peritoneal macrophages it will be determined cytokines and ROS production, mRNA expression of inflammatory citokynes, RAGE, AGE-R1 and NF-kB as wells as the NF-kB binding to the promotor of Ager gene.Findings will help to elucidate the mechanisms involved in the progression of inflammation in peritoneal and adipose tissue macrophages that may contribute to long term complications in DM.

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)

PINTO, PAULA R.; DA SILVA, KAROLLINE S.; IBORRA, RODRIGO T.; OKUDA, LIGIA S.; GOMES-KJERULF, DIEGO; FERREIRA, GUILHERME S.; MACHADO-LIMA, ADRIANA; ROCCO, DEBORA D. F. M.; NAKANDAKARE, EDNA R.; MACHADO, UBIRATAN F.; et al. Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice. FRONTIERS IN PHYSIOLOGY, v. 9, MAY 8 2018. (12/19112-0, 16/15603-0, 13/11084-0, 12/12088-7, 11/15153-1, 12/18724-2, 13/02854-7, 14/07617-6, 15/21072-5)

PINTO-JUNIOR, DANILO C.; SILVA, KAROLLINE S.; MICHALANI, MARIA L.; YONAMINE, CAIO Y.; ESTEVES, JOAO V.; FABRE, NELLY T.; THIEME, KARINA; CATANOZI, SERGIO; OKAMOTO, MARISTELA M.; SERAPHIM, PATRICIA M.; et al. Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression. SCIENTIFIC REPORTS, v. 8, MAY 25 2018. (12/20432-0, 16/15603-0, 16/25155-5, 12/18724-2, 13/00713-7, 14/17251-9)

THIEME, KARINA; VELOSO PEREIRA, BEATRIZ MARIA; DA SILVA, KAROLLINE S.; FABRE, NELLY T.; CATANOZI, SERGIO; PASSARELLI, MARISA; CORREA-GIANNELLA, MARIA LUCIA. Chronic advanced-glycation end products treatment induces TXNIP expression and epigenetic changes in glomerular podocytes in vivo and in vitro. Life Sciences, v. 270, APR 1 2021. (18/00573-4, 19/10583-0, 16/15603-0, 16/04591-1, 12/04831-1, 12/18724-2, 13/00713-7, 14/17251-9)

DA SILVA, KAROLLINE S.; PINTO, PAULA R.; FABRE, NELLY T.; GOMES, DIEGO J.; THIEME, KARINA; OKUDA, LIGIA S.; IBORRA, RODRIGO T.; FREITAS, VANESSA G.; SHIMIZU, MARIA H. M.; TEODORO, WALCY R.; et al. N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats. FRONTIERS IN PHYSIOLOGY, v. 8, SEP 22 2017. (16/15603-0, 12/12088-7, 11/15153-1, 12/04831-1, 12/18724-2, 14/17251-9, 13/02854-7)

THIEME, KARINA; DA SILVA, KAROLLINE S.; FABRE, NELLY T.; CATANOZI, SERGIO; MONTEIRO, MARIA BEATRIZ; SANTOS-BEZERRA, DANIELE PEREIRA; COSTA-PESSOA, JULIANA MARTINS; OLIVEIRA-SOUZA, MARIA; MACHADO, UBIRATAN F.; PASSARELLI, MARISA; et al. N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 40, n. 3-4, p. 608-620, 2016. (13/00713-7, 12/04831-1, 14/17251-9, 12/18724-2)

FABRE, NELLY T.; THIEME, KARINA; SILVA, KAROLLINE S.; CATANOZI, SERGIO; CAVALEIRO, ANA MERCEDES; PINTO, JR., DANILO A. C.; OKAMOTO, MARISTELA M.; MORAIS, MYCHEL RAONY P. T.; FALQUETTO, BARBARA; ZORN, TELMA M.; et al. Hormetic modulation of hepatic insulin sensitivity by advanced glycation end products. Molecular and Cellular Endocrinology, v. 447, n. C, p. 116-124, MAY 15 2017. (12/04831-1, 12/18724-2, 13/00713-7, 14/17251-9)

PINTO, PAULA RAMOS; FERRARETTO MOURA ROCCO, DEBORA DIAS; OKUDA, LIGIA SHIMABUKURO; MACHADO-LIMA, ADRIANA; CASTILHO, GABRIELA; DA SILVA, KAROLLINE SANTANA; GOMES, DIEGO JUVENAL; PINTO, RAPHAEL DE SOUZA; IBORRA, RODRIGO TALLADA; FERREIRA, GUILHERME DA SILVA; et al. Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta. LIPIDS IN HEALTH AND DISEASE, v. 14, SEP 16 2015. (12/19112-0, 11/04631-0, 12/12088-7, 11/15153-1, 12/04831-1, 12/18724-2, 13/02854-7)

Academic Publications

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

SILVA, Karolline Santana da. Advanced glycated albumin and insulin resistance in rats: focus on periepididimal adipose tissue and N-acetylcysteine actions. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.