Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway

Summary: Increasing evidence points toward vitamin D (VD) having lipometabolism and immune-related properties to protect against related metabolic diseases through influencing DNA methylation with inconsistent results. Simultaneously, its relatively precise molecular metabolism on the progression of...

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Main Authors: Yueqing Liang, Xueyi Jiang, Xinfeng Zhao, Tiantian Tang, Xiuqin Fan, Rui Wang, Mengyi Yang, Kemin Qi, Yi Zhang, Ping Li
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224024878
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author Yueqing Liang
Xueyi Jiang
Xinfeng Zhao
Tiantian Tang
Xiuqin Fan
Rui Wang
Mengyi Yang
Kemin Qi
Yi Zhang
Ping Li
author_facet Yueqing Liang
Xueyi Jiang
Xinfeng Zhao
Tiantian Tang
Xiuqin Fan
Rui Wang
Mengyi Yang
Kemin Qi
Yi Zhang
Ping Li
author_sort Yueqing Liang
collection DOAJ
description Summary: Increasing evidence points toward vitamin D (VD) having lipometabolism and immune-related properties to protect against related metabolic diseases through influencing DNA methylation with inconsistent results. Simultaneously, its relatively precise molecular metabolism on the progression of metabolic-associated fatty liver disease (MAFLD) remains uncertain. Here, we report an unprecedented role and possible mechanism for VD supplementation on the alleviation of high-fat diet (HFD)-induced MAFLD. Over time, our results demonstrated that metabolic disorders in the HFD-induced MAFLD were aggravated with a certain time-response dependence and accompanied by reduced VD metabolites. All these could be alleviated under sufficient VD supplementation in vivo and vitro. It was partially by inhibiting the expressions of DNMT1 to reverse the epigenetic patterns on the VD metabolism genes and TGFβR1, which ultimately triggered the TGFβ1/Smad3 pathway to result in the development of MAFLD. Furthermore, the protective effects of VD were weakened by the treatment with gene silencing of DNMT1.
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institution Kabale University
issn 2589-0042
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-eeba827c0e5a494388b41c932f3b682c2024-12-22T05:28:44ZengElsevieriScience2589-00422024-12-012712111262Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathwayYueqing Liang0Xueyi Jiang1Xinfeng Zhao2Tiantian Tang3Xiuqin Fan4Rui Wang5Mengyi Yang6Kemin Qi7Yi Zhang8Ping Li9Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaDepartment of Chemistry and Materials Science, Hebei University, Baoding City, Hebei Province 071002, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, ChinaDepartment of Chemistry and Materials Science, Hebei University, Baoding City, Hebei Province 071002, ChinaLaboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children’s Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China; Corresponding authorSummary: Increasing evidence points toward vitamin D (VD) having lipometabolism and immune-related properties to protect against related metabolic diseases through influencing DNA methylation with inconsistent results. Simultaneously, its relatively precise molecular metabolism on the progression of metabolic-associated fatty liver disease (MAFLD) remains uncertain. Here, we report an unprecedented role and possible mechanism for VD supplementation on the alleviation of high-fat diet (HFD)-induced MAFLD. Over time, our results demonstrated that metabolic disorders in the HFD-induced MAFLD were aggravated with a certain time-response dependence and accompanied by reduced VD metabolites. All these could be alleviated under sufficient VD supplementation in vivo and vitro. It was partially by inhibiting the expressions of DNMT1 to reverse the epigenetic patterns on the VD metabolism genes and TGFβR1, which ultimately triggered the TGFβ1/Smad3 pathway to result in the development of MAFLD. Furthermore, the protective effects of VD were weakened by the treatment with gene silencing of DNMT1.http://www.sciencedirect.com/science/article/pii/S2589004224024878dietary supplementmolecular biologycell biology
spellingShingle Yueqing Liang
Xueyi Jiang
Xinfeng Zhao
Tiantian Tang
Xiuqin Fan
Rui Wang
Mengyi Yang
Kemin Qi
Yi Zhang
Ping Li
Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway
iScience
dietary supplement
molecular biology
cell biology
title Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway
title_full Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway
title_fullStr Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway
title_full_unstemmed Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway
title_short Vitamin D alleviates HFD-induced hepatic fibrosis by inhibiting DNMT1 to affect the TGFβ1/Smad3 pathway
title_sort vitamin d alleviates hfd induced hepatic fibrosis by inhibiting dnmt1 to affect the tgfβ1 smad3 pathway
topic dietary supplement
molecular biology
cell biology
url http://www.sciencedirect.com/science/article/pii/S2589004224024878
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