Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice

被引：13

作者：

Choung, Sorim ^{[1
]}

Joung, Kyong Hye ^{[2
]}

You, Bo Ram ^{[2
]}

Park, Sang Ki ^{[2
]}

Kim, Hyun Jin ^{[2
]}

Ku, Bon Jeong ^{[1
,2
]}

机构：

[1] Chungnam Natl Univ, Coll Med, Dept Med Sci, Daejeon 35015, South Korea

[2] Chungnam Natl Univ, Coll Med, Dept Internal Med, Daejeon 35015, South Korea

来源：

PPAR RESEARCH | 2018年 / 2018卷

基金：

新加坡国家研究基金会;

关键词：

FATTY LIVER-DISEASE; ACTIVATED RECEPTOR-GAMMA; PPAR-GAMMA; AGONIST; PLACEBO; ALPHA;

D O I：

10.1155/2018/4292509

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid beta-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPAR gamma and phosphorylated PPAR gamma at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPAR alpha and diminished levels of PPAR gamma phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPAR alpha and posttranslational modification of PPAR gamma in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.

引用

页数：8

共 28 条

[1] Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice [J].