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.