1. Diosmetin Ameliorates Nonalcoholic Steatohepatitis through Modulating Lipogenesis and Inflammatory Response in a STAT1/CXCL10-Dependent Manner.
- Author
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Luo N, Yang C, Zhu Y, Chen Q, and Zhang B
- Subjects
- Animals, Chemokine CXCL10 genetics, Humans, Liver drug effects, Liver immunology, Male, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease genetics, Non-alcoholic Fatty Liver Disease immunology, Non-alcoholic Fatty Liver Disease physiopathology, STAT1 Transcription Factor genetics, Signal Transduction physiology, Sterol Regulatory Element Binding Protein 1 genetics, Sterol Regulatory Element Binding Protein 1 immunology, Chemokine CXCL10 immunology, Flavonoids administration & dosage, Lipogenesis drug effects, Non-alcoholic Fatty Liver Disease drug therapy, STAT1 Transcription Factor immunology
- Abstract
Nonalcoholic steatohepatitis (NASH) is an inflammatory lipotoxic disorder characterized by lipid accumulation and inflammation. Diosmetin (Dios), a flavonoid, has an active effect against nonalcoholic fatty liver disease, whereas its effect on NASH remains elusive. To investigate the effects of Dios on lipogenesis and inflammatory response and explore the molecular mechanisms of Dios on NASH, mice induced by high-fat diet (HFD), HepG2 cells stimulated by palmitic acid (PA), transcriptome sequencing, and molecular biological experiments were used. We show, by pathological analysis (HE, Oli Red O, and Masson staining) and biochemical parameters (TC, TG, LDL-C, ALT, and AST), Dios alleviated liver lipid accumulation and inflammatory injury. According to liver RNA-Seq analysis, CXCL10 and STAT1 were assumed to be the key target genes of Dios on NASH. Significantly, Dios regulated STAT1/CXCL10 signal pathway and further attenuated NASH via regulating the expression of LXRα/β, SREBP-1c, CHREBP, and NF-κB. In conclusion, Dios is proposed to alleviate NASH through suppression of lipogenesis and inflammatory response via a STAT1/CXCL10-dependent pathway.
- Published
- 2021
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