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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.)

GQ-11: A new PPAR agonist improves obesity-induced metabolic alterations in LDLr-/- mice

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Author(s):
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Silva, Jacqueline C. [1] ; de Oliveir, Edson M. [1] ; Turato, Walter M. [1] ; Trossini, Gustavo H. G. [2] ; Maltarollo, Vinicius G. [2] ; Pitta, Marina G. R. [3] ; Pitta, Ivan R. [3] ; de las Heras, Beatriz [4] ; Bosca, Lisardo [5] ; Rudnicki, Martina [1] ; Abdalla, Dulcineia S. P. [1]
Total Authors: 11
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, Sao Paulo, SP - Brazil
[3] Univ Fed Pernambuco, Core Therapeut Innovat, Recife, PE - Brazil
[4] Univ Complutense Madrid, Fac Pharm, Dept Pharmacol, Madrid - Spain
[5] CSIC UAM, Inst Invest Biomed Alberto Sols, Madrid - Spain
Total Affiliations: 5
Document type: Journal article
Source: International Journal of Obesity; v. 42, n. 5, p. 1062-1072, JUN 2018.
Web of Science Citations: 3
Abstract

Background Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics. Objective To assess the effects of a new thiazolidine compound-GQ-11-on obesity and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient (LDLr-/-) mice. Methods Molecular docking simulations of GQ-11, PPARy and PPARy structures were performed. Male C57BL/6J LDLr-/- mice fed a diabetogenic diet for 24 weeks were treated with vehicle, GQ-11 or pioglitazone or (20 mg/kg/day) for 28 days by oral gavage. Glucose tolerance test, insulin, HOMA-IR, adipokines (leptin, adiponectin) and the lipid profile were assessed after treatment. Adipose tissue was analysed by X-ray analysis and morphometry; gene and protein expression were evaluated by real-time PCR and western blot, respectively. Results GQ-11 showed partial agonism to PPAR gamma and PPAR alpha. In vivo, treatment with GQ-11 ameliorated insulin sensitivity and did not modify subcutaneous adipose tissue and body weight gain. In addition, GQ-11 restored adipokine imbalance induced by a diabetogenic diet and enhanced Glut-4 expression in the adipose tissue. Improved insulin sensitivity was also associated with lower levels of MCP-1 and higher levels of IL-10. Furthermore, GQ-11 reduced triglycerides and VLDL cholesterol and increased HDL-cholesterol by upregulation of Apoal and Abcal gene expression in the liver. Conclusion GQ-11 is a partial/dual PPAR alpha/gamma agonist that demonstrates anti-diabetic effects. Additionally, it improves the lipid profile and ameliorates chronic inflammation associated with obesity in atherosclerosis-prone mice. (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