Volume 7 Supplement 1

20th Brazilian Diabetes Society Congress

Open Access

GW501516, a PPAR-BETA/DELTA agonist, improves inflammatory pathways in the kidney of high-fructose fed mice

  • D'Angelo Carlo Magliano1,
  • Isabele Bringhenti Sarmento1,
  • Vanessa de Souza Mello1Email author,
  • Carlos Alberto Mandarim de Lacerda1 and
  • Marcia Barbosa Aguila1
Diabetology & Metabolic Syndrome20157(Suppl 1):A121

https://doi.org/10.1186/1758-5996-7-S1-A121

Published: 11 November 2015

Background

Angiotensin-II type 1 receptor (AT1r) high activation is closely linked to a low-grade inflammation and oxidative stress that yield impaired renal function and, consequently, chronic kidney disease (CKD).

Objectives

Therefore, the aim of this study was to verify if GW501516 could improve damage in the kidney of mice with high activation of AT1r.

Materials and methods

To induce high activation of this receptor, mice were fed a high-fructose diet for eight weeks. The control group only received standard-chow (SC). After, the animals were randomly divided into four groups and the administration of GW501516 started and lasted three weeks. Morphological variables and urinary and plasmatic determinations were assessed. Renin and angiotensin converting enzyme (ACE)/AT1r axis protein and gene expression were evaluated as well as inflammatory cytokines and proteins. Also, the protein and gene expression of the antioxidant enzymes were verified.

Results

GW501516 activated PPAR-beta/delta and its target genes PDK4 and CPT-1. Despite showing no effects either on ACE/AT1r axis or renin expression, GW501516 improved the inflammatory state in the kidney. It elicits an expressive reduction in the expression of inflammatory genes such as IL-1β, IL-6, MCP-1 and Cd68, irrespective of AT1 downregulation. However, no differences were found in oxidative stress.

Conclusions

We conclude that GW501516, a PPAR-beta/delta agonist, acts downstream AT1r activation, improving inflammatory pathways in the kidney of high-fructose fed model.

Authors’ Affiliations

(1)
Universidade do Estado do Rio de Janeiro

Copyright

© Magliano et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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