Treatment with PPARδ agonist alleviates non-alcoholic fatty liver disease by modulating glucose and fatty acid metabolic enzymes in a rat model

Li,Xiuli; Li,Jin; Lu,Xiaolan; Ma,Huihui; Shi,Haitao; Li,Hong; Xie,Danhong; Dong,Lei; Liang,Chunlian

doi:10.3892/ijmm.2015.2270

Treatment with PPARδ agonist alleviates non-alcoholic fatty liver disease by modulating glucose and fatty acid metabolic enzymes in a rat model

Authors:
- Xiuli Li
- Jin Li
- Xiaolan Lu
- Huihui Ma
- Haitao Shi
- Hong Li
- Danhong Xie
- Lei Dong
- Chunlian Liang
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Affiliations: Department of Geriatrics, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: July 1, 2015 https://doi.org/10.3892/ijmm.2015.2270
Pages: 767-775

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition which is associated with certain features of metabolic syndrome and insulin resistance. Peroxisome proliferator‑activated receptor (PPAR)δ is an important regulator of energy metabolism and insulin resistance in diabetes. However, the function of PPARδ in NAFLD has not yet been fully elucidated. In the present study, in order to explore the function of PPARδ in NAFLD, we created a rat model of NALFD induced by a high-fat diet (HFD) and treated the rats with GW501516, a PPARδ agonist. We found that the lipid levels decreased, and hepatocellular ballooning and inflammatory cell infiltration were also significantly decreased following treatment of the rats with GW501516 compared to the untreated rats. Treatment with GW501516 also significantly decreased the homeostasis model assessment of insulin resistance (HOMA-IR) index, as well as the low‑density lipoprotein (LDL) levels. In addition, treatment with GW501516 increased the levels of insulin‑like growth factor‑1 (IGF-1) and high‑density lipoprotein (HDL) compared to the HFD group. Furthermore, the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) in the HFD group were all restored to the normal control levels following treatment with GW501516. RT‑qPCR and immunohistochemical staining revealed that the expression levels of sterol regulatory element binding protein‑1c (SREBP‑1c) and glucose transporter 2 (GLUT‑2) were both restored to normal control levels following treatment with GW501516. Also, the levels of enzymes related to lipid metabolism were increased following treatment with GW501516. In conclusion, our findings demonstrate that treatment with GW501516 alleviates NAFLD by modulating glucose and fatty acid metabolism.

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