[PMID]: | 28665967 |
[Au] Autor: | Ji W; Zhao M; Wang M; Yan W; Liu Y; Ren S; Lu J; Wang B; Chen L |
[Ad] Endereço: | Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China. |
[Ti] Título: | Effects of canagliflozin on weight loss in high-fat diet-induced obese mice. |
[So] Source: | PLoS One;12(6):e0179960, 2017. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined. Signaling molecules, including diacylgycero1 acyltransferase-2 (DGAT2), peroxisome proliferation receptor alpha-1 (PPARα1), PPARγ1, PPARγ2 mRNA levels and the protein expression of SGLT2 were evaluated. Canagliflozin reduced body weight, especially the high-dose canagliflozin, and resulted in increased body weight loss compared with orlistat. Moreover, canagliflozin reduced the liver weight and the ratio of liver weight to body weight, lowered the serum levels of TC and TG, and ameliorated liver steatosis. During the canagliflozin treatment, SGLT2, DGAT2, PPARγ1 and PPARγ2 were inhibited, and PPARα1 was elevated in the liver tissues. This finding may explain why body weight was reduced and secondary liver injury was ameliorated in response to canagliflozin. Together, the results suggest that canagliflozin may be a potential anti-obesity strategy. |
[Mh] Termos MeSH primário: |
Canagliflozina/farmacologia Dieta Hiperlipídica Hipoglicemiantes/uso terapêutico Obesidade/terapia Perda de Peso/efeitos dos fármacos
|
[Mh] Termos MeSH secundário: |
Animais Colesterol/sangue Diacilglicerol O-Aciltransferase/metabolismo Fígado/efeitos dos fármacos Fígado/patologia Camundongos Camundongos Endogâmicos C57BL Obesidade/enzimologia Obesidade/etiologia Obesidade/metabolismo Receptores Ativados por Proliferador de Peroxissomo/metabolismo Triglicerídeos/sangue
|
[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Hypoglycemic Agents); 0 (Peroxisome Proliferator-Activated Receptors); 0 (Triglycerides); 0SAC974Z85 (Canagliflozin); 97C5T2UQ7J (Cholesterol); EC 2.3.1.20 (DGAT2 protein, mouse); EC 2.3.1.20 (Diacylglycerol O-Acyltransferase) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171002 |
[Lr] Data última revisão:
| 171002 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170701 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0179960 |
|
|