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Ying-Bin Hu, 1 Xin-Yu Liu, 2 Wei Zhan 1
1 Department of Gastroenterology, Puai Hospital (Wuhan Fourth Hospital ), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; 2 Cancer Science Institute, National University of Singapore, Singapore
Introduction: Nonalcoholic steatohepatitis (NASH) is largely due to the deregulation of metabolism and inflammation of the body. liver. Bile acids and their Farnesoid X receptor (FXR) receptor play an essential role in the development of the disease. Here, we investigated whether INT-767, the newly identified dual FXR / TGR5 agonist, can protect the rat from liver injury during NASH.
Material and Methods: NASH model was established by feeding male SD rats with high-fatigue for 16 weeks. INT-767 was administered by gavage to NASH rats from week 13 to week 16. After 16 weeks, liver and serum were harvested, and bile acids, glucose and lipid metabolism, Hepatic lesions and histological features were evaluated
. Results: INT-767 treatment significantly attenuates high-fat liver damage, characterized by lipid accumulation and hepatic infiltration of immune cells. INT-767 restores lipid, glucose metabolism to a normal level, attenuates insulin resistance by positively regulating FXR level and reversing the deregulation of its target genes in hepatic metabolism. Molecularly INT-767 also attenuates the pro-inflammatory response by suppressing the TNF-α and NF-κB signaling pathway.
Conclusion: INT-767 may be an interesting candidate for a new potential strategy on the treatment of NASH
Keywords: farnesoid X receptor agonist, nonalcoholic steatohepatitis, INT-767 , transmembrane receptor coupled to G protein 5
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