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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

New PPAR gamma partial agonist improves obesity-induced metabolic alterations and atherosclerosis in LDLr-/- mice

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Author(s):
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Silva, Jacqueline C. [1] ; Cesar, Fernanda A. [1] ; de Oliveira, Edson M. [1] ; Turato, Walter M. [1] ; Tripodi, Gustavo L. [1] ; Castilho, Gabriela [2] ; Machado-Lima, Adriana [2] ; de las Heras, Beatriz [3] ; Bosca, Lisardo [4] ; Rabello, Marcelo M. [5] ; Hernandes, Marcelo Z. [5] ; Pitta, Marina G. R. [6] ; Pitta, Ivan R. [6] ; Passarelli, Marisa [2] ; Rudnicki, Martina [1] ; Abdalla, Dulcineia S. P. [1]
Total Authors: 16
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Lipids Lab LIM 10, Sao Paulo, SP - Brazil
[3] Univ Complutense Madrid, Dept Pharmacol, Madrid - Spain
[4] Inst Invest Biomed Alberto Sols CSIC UAM, Madrid - Spain
[5] Univ Fed Pernambuco, Dept Pharmaceut Sci, Recife, PE - Brazil
[6] Univ Fed Pernambuco, Core Therapeut Innovat, Recife, PE - Brazil
Total Affiliations: 6
Document type: Journal article
Source: PHARMACOLOGICAL RESEARCH; v. 104, p. 49-60, FEB 2016.
Web of Science Citations: 15
Abstract

Peroxisome proliferator-activated receptor gamma (PPAR gamma) regulates multiple pathways involved in the pathogenesis of obesity and atherosclerosis. Here, we evaluated the therapeutic potential of GQ-177, a new thiazolidinedione, on diet-induced obesity and atherosclerosis. The intermolecular interaction between PPAR gamma and GQ-177 was examined by virtual docking and PPAR activation was determined by reporter gene assay identifying GQ-177 as a partial and selective PPAR gamma agonist. For the evaluation of biological activity of GQ-177, low-density lipoprotein receptor-deficient (LDLr-/-) C57/BL6 mice were fed either a high fat diabetogenic diet (diet-induced obesity), or a high fat atherogenic diet, and treated with vehicle, GQ-177 (20 mg/kg/day), pioglitazone (20 mg/kg/day, diet-induced obesity model) or rosiglitazone (15 mg/kg/day, atherosclerosis model) for 28 days. In diet-induced obesity mice, GQ-177 improved insulin sensitivity and lipid profile, increased plasma adiponectin and GLUT4 mRNA in adipose tissue, without affecting body weight, food consumption, fat accumulation and bone density. Moreover, GQ-177 enhanced hepatic mRNA levels of proteins involved in lipid metabolism. In the atherosclerosis mice, GQ-177 inhibited atherosclerotic lesion progression, increased plasma HDL and mRNA levels of PPAR), and ATP-binding cassette A1 in atherosclerotic lesions. GQ-177 acts as a partial PPAR gamma agonist that improves obesity-associated insulin resistance and dyslipidemia with atheroprotective effects in LDLr-/- mice. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 12/14360-6 - Investigation of the effects of new thiazolidinediones in animal model of metabolic syndrome.
Grantee:Jacqueline Cavalcante Silva
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 12/51316-5 - Study of the activity of biodrugs, PPARs agonists and natural products with therapeutic potential in atherosclerosis
Grantee:Dulcineia Saes Parra Abdalla
Support Opportunities: Research Projects - Thematic Grants