1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model
We studied the potential protective effects of 1,25-dihydroxyvitamin D3 (1,25 VD3) supplementation on liver damage induced by a choline-deficient (CD) diet in rats, where impaired liver function leads to decreased 25-hydroxyvitamin D3 levels, the precursor for the active 1,25 VD3. The CD diet reduce...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1528768/full |
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| author | Mei Liu Xiang-Zhun Song Liu Yang Yu-Hui Fang Liu Lan Jing-Shu Cui Xiao-Chen Lu Hai-Yang Zhu Lin-Hu Quan Hong-Mei Han |
| author_facet | Mei Liu Xiang-Zhun Song Liu Yang Yu-Hui Fang Liu Lan Jing-Shu Cui Xiao-Chen Lu Hai-Yang Zhu Lin-Hu Quan Hong-Mei Han |
| author_sort | Mei Liu |
| collection | DOAJ |
| description | We studied the potential protective effects of 1,25-dihydroxyvitamin D3 (1,25 VD3) supplementation on liver damage induced by a choline-deficient (CD) diet in rats, where impaired liver function leads to decreased 25-hydroxyvitamin D3 levels, the precursor for the active 1,25 VD3. The CD diet reduced serum 25 VD3 levels and increased liver enzymes, indicative of liver damage. Conversely, 1,25 VD3 supplementation alleviated liver damage, reducing liver enzymes and improving histopathological features characteristic of non-alcoholic steatohepatitis (NASH). Oxidative stress and inflammation were mitigated by 1,25 VD3, as evidenced by decreased malondialdehyde and nuclear factor kappa B (NF-κB) expression, and increased total antioxidant capacity (TAOC). 1,25 VD3 also enhanced fatty acid metabolism by increasing peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase-1 (CPT-1) expression, promoting lipid transport and oxidation. Additionally, 1,25 VD3 supplementation modulated inflammation by increasing PPARγ expression, reducing NF-κB expression, and decreasing pro-inflammatory cytokines (TNF-α, IL-1β). Anti-inflammatory cytokines (IL-10, IL-4) were increased, and macrophage polarization was shifted towards an anti-inflammatory M2 phenotype. Moreover, 1,25 VD3 upregulated CYP2J3, a cytochrome P450 epoxygenase that converts arachidonic acid to anti-inflammatory epoxyeicosatrienoic acids (EETs) and decreased soluble epoxide hydrolase activity, likely contributing to increased EET levels. Correlation studies revealed positive associations between 1,25 VD3 supplementation, CYP2J3 expression, EETs, as well as negative correlations with NF-κB and TNF-α. PPARα expression positively correlated with TAOC and CPT-1, while PPARγ expression negatively correlated with inflammatory markers. These findings demonstrate the therapeutic potential of 1,25 VD3 in alleviating NASH through regulation of fatty acid metabolism, inflammation, and oxidative stress. |
| format | Article |
| id | doaj-art-976bae141a2742fba09a3faf82839ef6 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-976bae141a2742fba09a3faf82839ef62025-08-20T03:41:51ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-03-011610.3389/fendo.2025.152876815287681,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat modelMei Liu0Xiang-Zhun Song1Liu Yang2Yu-Hui Fang3Liu Lan4Jing-Shu Cui5Xiao-Chen Lu6Hai-Yang Zhu7Lin-Hu Quan8Hong-Mei Han9Department of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, Jilin, ChinaDepartment of Gastroenterology, Jilin Provincial People’s Hospital, Changchun, Jilin, ChinaDepartment of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, ChinaDepartment of Dermatology, Fuyang People’s Hospital of Anhui Medical University, Fuyang, Anhui, ChinaDepartment of Pathology, Affiliated Hospital of Yanbian University, Yanji, Jilin, ChinaDepartment of Pathology, Affiliated Hospital of Yanbian University, Yanji, Jilin, ChinaDepartment of Gastroenterology, Jimo District People’s Hospital, Qingdao, Shandong, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, Jilin, ChinaDepartment of College of Pharmacy, Yanbian University, Yanji, Jilin, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, Jilin, ChinaWe studied the potential protective effects of 1,25-dihydroxyvitamin D3 (1,25 VD3) supplementation on liver damage induced by a choline-deficient (CD) diet in rats, where impaired liver function leads to decreased 25-hydroxyvitamin D3 levels, the precursor for the active 1,25 VD3. The CD diet reduced serum 25 VD3 levels and increased liver enzymes, indicative of liver damage. Conversely, 1,25 VD3 supplementation alleviated liver damage, reducing liver enzymes and improving histopathological features characteristic of non-alcoholic steatohepatitis (NASH). Oxidative stress and inflammation were mitigated by 1,25 VD3, as evidenced by decreased malondialdehyde and nuclear factor kappa B (NF-κB) expression, and increased total antioxidant capacity (TAOC). 1,25 VD3 also enhanced fatty acid metabolism by increasing peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase-1 (CPT-1) expression, promoting lipid transport and oxidation. Additionally, 1,25 VD3 supplementation modulated inflammation by increasing PPARγ expression, reducing NF-κB expression, and decreasing pro-inflammatory cytokines (TNF-α, IL-1β). Anti-inflammatory cytokines (IL-10, IL-4) were increased, and macrophage polarization was shifted towards an anti-inflammatory M2 phenotype. Moreover, 1,25 VD3 upregulated CYP2J3, a cytochrome P450 epoxygenase that converts arachidonic acid to anti-inflammatory epoxyeicosatrienoic acids (EETs) and decreased soluble epoxide hydrolase activity, likely contributing to increased EET levels. Correlation studies revealed positive associations between 1,25 VD3 supplementation, CYP2J3 expression, EETs, as well as negative correlations with NF-κB and TNF-α. PPARα expression positively correlated with TAOC and CPT-1, while PPARγ expression negatively correlated with inflammatory markers. These findings demonstrate the therapeutic potential of 1,25 VD3 in alleviating NASH through regulation of fatty acid metabolism, inflammation, and oxidative stress.https://www.frontiersin.org/articles/10.3389/fendo.2025.1528768/fullvitamin D3non-alcoholic steatohepatitisCYP450inflammationmacrophage |
| spellingShingle | Mei Liu Xiang-Zhun Song Liu Yang Yu-Hui Fang Liu Lan Jing-Shu Cui Xiao-Chen Lu Hai-Yang Zhu Lin-Hu Quan Hong-Mei Han 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model Frontiers in Endocrinology vitamin D3 non-alcoholic steatohepatitis CYP450 inflammation macrophage |
| title | 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model |
| title_full | 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model |
| title_fullStr | 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model |
| title_full_unstemmed | 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model |
| title_short | 1,25-dihydroxyvitamin D3 improves non-alcoholic steatohepatitis phenotype in a diet-induced rat model |
| title_sort | 1 25 dihydroxyvitamin d3 improves non alcoholic steatohepatitis phenotype in a diet induced rat model |
| topic | vitamin D3 non-alcoholic steatohepatitis CYP450 inflammation macrophage |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1528768/full |
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