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

Imagem de Miniatura
Arquivos
art_SILVA_New_PPAR_gamma_partial_agonist_improves_obesityinduced_metabolic_2016.PDF (2.56 MB)
Citações na Scopus
25
Tipo de produção
article
Data de publicação
2016
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Autores
SILVA, Jacqueline C.
CESAR, Fernanda A.
OLIVEIRA, Edson M. de
TURATO, Walter M.
TRIPODI, Gustavo L.
CASTILHO, Gabriela
HERAS, Beatriz de las
BOSCA, Lisardo
RABELLO, Marcelo M.
Citação
PHARMACOLOGICAL RESEARCH, v.104, p.49-60, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Atherosclerosis, Diabetes, Obesity, PPAR gamma, Thiazolidinediones
URI
https://observatorio.fm.usp.br/handle/OPI/13866
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/10
Artigos e Materiais de Revistas Científicas - ODS/03