title: LPSF/GQ-02 inhibits the development of hepatic steatosis and inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD).
abstract: Non-alcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extends from simple steatosis to non-alcoholic steatohepatitis. Although the pathogenesis of NAFLD remains undefined, it is recognized that insulin resistance is present in almost all patients who develop this disease. Thiazolidinediones (TZDs) act as an insulin sensitizer and have been used in the treatment of patients with type 2 diabetes and other insulin-resistant conditions, including NAFLD. Hence, therapy of NAFLD with insulin-sensitizing drugs should ideally improve the key hepatic histological changes, while also reducing cardiometabolic and cancer risks. Controversially, TZDs are associated with the development of cardiovascular events and liver problems. Therefore, there is a need for the development of new therapeutic strategies to improve liver function in patients with chronic liver diseases. The aim of the present study was to assess the therapeutic effects of LPSF/GQ-02 on the liver of LDLR-/- mice after a high-fat diet. Eighty male mice were divided into 4 groups and two different experiments: 1-received a standard diet; 2-fed with a high-fat diet (HFD); 3-HFD+pioglitazone; 4-HFD+LPSF/GQ-02. The experiments were conducted for 10 or 12 weeks and in the last two or four weeks respectively, the drugs were administered daily by gavage. The results obtained with an NAFLD murine model indicated that LPSF/GQ-02 was effective in improving the hepatic architecture, decreasing fat accumulation, reducing the amount of collagen, decreasing inflammation by reducing IL-6, iNOS, COX-2 and F4 / 80, and increasing the protein expression of IκBα, cytoplasmic NFκB-65, eNOS and IRS-1 in mice LDLR -/-. These results suggest a direct action by LPSF/GQ-02 on the factors that affect inflammation, insulin resistance and fat accumulation in the liver of these animals. Further studies are being conducted in our laboratory to investigate the possible mechanism of action of LPSF/GQ-02 on hepatic lipid metabolism.
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Amanda Karolina
authors: AK
authors: Soares e Silva
authors: Laboratório de Análises Clínicas da Universidade de Pernambuco, Pernambuco, Recife, Brazil.
authors: Dilênia
authors: D
authors: de Oliveira Cipriano Torres
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Fabiana Oliveira
authors: FO
authors: dos Santos Gomes
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Bruna
authors: B
authors: dos Santos Silva
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Edlene
authors: E
authors: Lima Ribeiro
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Amanda
authors: A
authors: Costa Oliveira
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Laise Aline Martins
authors: LA
authors: dos Santos
authors: Laboratório de planejamento e síntese de fármacos, Universidade federal de Pernambuco, Pernambuco, Recife, Brazil.
authors: Maria do Carmo Alves
authors: Mdo C
authors: de Lima
authors: Laboratório de planejamento e síntese de fármacos, Universidade federal de Pernambuco, Pernambuco, Recife, Brazil.
authors: Ivan da Rocha
authors: Ida R
authors: Pitta
authors: Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (FIOCRUZ), Pernambuco, Recife, Brazil.
authors: Christina Alves
authors: CA
authors: Peixoto
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077205:Pioglitazone; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000032:analysis / Q000097:blood
chemical_list: C581247:5-(4-chlorobenzylidene)-3-(4-methylbenzyl)thiazolidine-2,4-dione; C464944:Emr4 protein, mouse; D020672:I-kappa B Proteins; D015850:Interleukin-6; C000606205:Nfkbia protein, mouse; D011973:Receptors, LDL; D045162:Thiazolidinediones; D014280:Triglycerides; D000072000:NF-KappaB Inhibitor alpha; D004815:Epidermal Growth Factor; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000077205:Pioglitazone