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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Obesity; v. 42, n. 5, p. 1062-1072, JUN 2018.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 12/14360-6 - Investigação dos efeitos de novos derivados tiazolidínicos em modelo animal de síndrome metabólica.
• Beneficiário: Jacqueline Cavalcante Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/51316-5 - Investigação da atividade de biofármacos, agonistas de PPARs e produtos naturais com potencial terapêutico na aterosclerose
• Beneficiário: Dulcineia Saes Parra Abdalla
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/53072-3 - Novas tiozolidinadionas: propriedades angiogenicas e efeitos em celulas endoteliais
• Beneficiário: Martina Rudnicki
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado