Xiaoyuan Chen1,2, Chao Liu3, Litao Ruan4. 1. Department of Ultrasound, Women and Children's Hospital of Northwest, Xi'an, 710061, Shaanxi, China. 2. Department of Ultrasound, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China. 3. Department of General Surgery, Affiliated Hospital of Yan'an University, Yan'an, 716000, Shaanxi, China. 4. Department of Ultrasound, Women and Children's Hospital of Northwest, Xi'an, 710061, Shaanxi, China. ruanlitao@163.com.
Abstract
BACKGROUND: GPR120 plays a crucial role in insulin sensitization, inflammatory responses and obesity and is considered as an attractive potential target for the treatment of metabolic dysfunctions. However, the mechanisms of GPR120 agonist III in NAFLD/NASH treatment are still unclear. AIMS: We aimed to evaluate the effect and molecular mechanisms of GPR120 agonist III on NASH, and search for future treatments of human NAFLD/NASH. METHODS: The effects of GPR120 agonist III on steatohepatitis were evaluated in mice fed with HFHC diet and MCD diet. The ultrastructural changes of ER were assessed by TEM. Hepatic ROS production was evaluated by DHE staining. Apoptosis and macrophage infiltration were determined by IHC staining. Inflammatory cytokines secretion were examined using mouse XL cytokine array. RESULTS: GPR120 agonist III significantly suppressed macrophage infiltration and ROS production and reversed hepatic inflammation, ER stress and apoptosis in dietary-induced steatohepatitis. CONCLUSION: GPR120 agonist III will be an attractive treatment method in steatohepatitis, which opens up a new sight for future treatments of human NAFLD/NASH.
BACKGROUND:GPR120 plays a crucial role in insulin sensitization, inflammatory responses and obesity and is considered as an attractive potential target for the treatment of metabolic dysfunctions. However, the mechanisms of GPR120 agonist III in NAFLD/NASH treatment are still unclear. AIMS: We aimed to evaluate the effect and molecular mechanisms of GPR120 agonist III on NASH, and search for future treatments of human NAFLD/NASH. METHODS: The effects of GPR120 agonist III on steatohepatitis were evaluated in mice fed with HFHC diet and MCD diet. The ultrastructural changes of ER were assessed by TEM. Hepatic ROS production was evaluated by DHE staining. Apoptosis and macrophage infiltration were determined by IHC staining. Inflammatory cytokines secretion were examined using mouse XL cytokine array. RESULTS:GPR120 agonist III significantly suppressed macrophage infiltration and ROS production and reversed hepatic inflammation, ER stress and apoptosis in dietary-induced steatohepatitis. CONCLUSION:GPR120 agonist III will be an attractive treatment method in steatohepatitis, which opens up a new sight for future treatments of human NAFLD/NASH.
Entities:
Keywords:
ER stress; GPR120 agonist; Inflammation; Nonalcoholic steatohepatitis