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Artigo Produção Nacional Revisado por pares
BIBTEX RIS

Effects of the new thiazolidine derivative LPSF/GQ-02 on hepatic lipid metabolism pathways in non-alcoholic fatty liver disease (NAFLD)

2016; Elsevier BV; Volume: 788; Linguagem: Inglês

10.1016/j.ejphar.2016.06.043

ISSN

1879-0712

Autores

Shyrlene Meiry Rocha Araújo, Amanda Soares e Silva, Fabiana Gomes, Edlene Lima Ribeiro, Wilma Helena de Oliveira, A. C. Oliveira, Ingrid Tavares de Lima, Maria do Carmo Alves de Lima, Ivan da Rocha Pitta, Christina Alves Peixoto,

Tópico(s)

Diet, Metabolism, and Disease

Resumo

Non-alcoholic fatty liver disease (NAFLD) is considered the most common manifestation of metabolic syndrome. One of its most important features is the accumulation of triglycerides in the hepatocyte cells. Thiazolidinediones (TZDs) act as insulin sensitizers and are used to treat patients with type 2 diabetes and other conditions that are resistant to insulin, such as hepatic steatosis. Controversially, TZDs are also associated with the development of cardiovascular events and liver problems. For this reason, new therapeutic strategies are necessary to improve liver function in patients with chronic liver diseases. The aim of the present study was to evaluate the effects of LPSF/GQ-02 on the liver lipid metabolism in a murine model of NAFLD. Eighty male LDLR-/- mice were divided into 3 groups: 1–fed with a high-fat diet (HFD); 2–HFD+Pioglitazone (20 mg/kg/day); 3–HFD+LPSF/GQ-02 (30 mg/kg/day). The experiments lasted 12 weeks and drugs were administered daily by gavage in the final four weeks. The liver was processed for optical microscopy, Oil Red O, immunohistochemistry, immunofluorescence and western blot analysis. LPSF/GQ-02 effectively decreased fat accumulation, increased the hepatic levels of p-AMPK, FoxO1, ATGL, p-ACC and PPARα, and reduced the expression of LXRα, SREBP-1c and ACC. These results suggest that LPSF/GQ-02 acts directly on the hepatic lipid metabolism through the activation of the PPAR-α/AMPK/FoxO1/ATGL lipolytic pathway, and the inhibition of the AMPK/LXR/SREBP-1c/ACC/FAS lipogenic pathway.

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