GQ-11: A new PPAR agonist improves obesity-induced metabolic alterations in LDLr-/- mice.
Int J Obes (Lond)
; 42(5): 1062-1072, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29453462
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, 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.RESULTS:
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.CONCLUSION:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Receptores Ativados por Proliferador de Peroxissomo
/
Tiazolidinas
/
Indóis
/
Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Int J Obes (Lond)
Assunto da revista:
METABOLISMO
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil