A new mechanism of thyroid hormone receptor β agonists ameliorating nonalcoholic steatohepatitis by inhibiting intestinal lipid absorption via remodeling bile acid profiles.
Autor: | Sun K; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.; University of Chinese Academy of Sciences, Beijing, 100049, China., Zhu NL; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Huang SL; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Qu H; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Gu YP; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Qin L; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China., Liu J; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. jia.liu@simm.ac.cn., Leng Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. yleng@simm.ac.cn.; University of Chinese Academy of Sciences, Beijing, 100049, China. yleng@simm.ac.cn. |
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Jazyk: | angličtina |
Zdroj: | Acta pharmacologica Sinica [Acta Pharmacol Sin] 2024 May 24. Date of Electronic Publication: 2024 May 24. |
DOI: | 10.1038/s41401-024-01303-x |
Abstrakt: | Excessive dietary calories lead to systemic metabolic disorders, disturb hepatic lipid metabolism, and aggravate nonalcoholic steatohepatitis (NASH). Bile acids (BAs) play key roles in regulating nutrition absorption and systemic energy homeostasis. Resmetirom is a selective thyroid hormone receptor β (THRβ) agonist and the first approved drug for NASH treatment. It is well known that the THRβ activation could promote intrahepatic lipid catabolism and improve mitochondrial function, however, its effects on intestinal lipid absorption and BA compositions remain unknown. In the present study, the choline-deficient, L-amino acid defined, high-fat diet (CDAHFD) and high-fat diet plus CCl (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.) |
Databáze: | MEDLINE |
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