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

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Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics.


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.


Molecular docking simulations of GQ-11, PPARα and PPARγ 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.


GQ-11 showed partial agonism to PPARγ and PPARα. 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 Apoa1 and Abca1 gene expression in the liver.


GQ-11 is a partial/dual PPARα/γ agonist that demonstrates anti-diabetic effects. Additionally, it improves the lipid profile and ameliorates chronic inflammation associated with obesity in atherosclerosis-prone mice.

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This study was supported by the São Paulo Research Foundation (FAPESP grant 2012/51316-5 to DSPA) and the National Council for Scientific and Technological Development (National Institute of Science and Technology for Pharmaceutical Innovation (INCT_if/CNPq) grant 573663/2008-4 to IRP and CNPq/MICCIN grant BFU2011-2476 to DSPA, LB and BdlH). JCS was supported by a FAPESP fellowship (2012/14360-6), and MR was supported by FAPESP (2009/53072-3) and CNPq (151568/2013-8) fellowships.

Author information


  1. Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil

    • Jacqueline C. Silva
    • , Edson M. de Oliveira
    • , Walter M. Turato
    • , Martina Rudnicki
    •  & Dulcineia S. P. Abdalla
  2. Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil

    • Gustavo H. G. Trossini
    •  & Vinícius G. Maltarollo
  3. Core of Therapeutic Innovation, Federal University of Pernambuco, Recife, PE, Brazil

    • Marina G. R. Pitta
    •  & Ivan R. Pitta
  4. Department of Pharmacology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain

    • Beatriz de las Heras
  5. Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain

    • Lisardo Boscá


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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Dulcineia S. P. Abdalla.

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