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Title:
Vitamin D supplementation alleviates high fat diet-induced metabolic associated fatty liver disease by inhibiting ferroptosis pathway | European Journal of Nutrition
Description:
Purpose Recently, a significant negative correlation has been found between vitamin D (VD) and metabolic associated fatty liver disease (MAFLD), suggesting a potential beneficial role of VD in preventing of MAFLD, while underscoring the importance of exploring its mechanisms. Methods The experiment comprised two parts: male C57BL/6J mice (6 weeks) were fed a high-fat diet (HFD) and intraperitoneally injected with vitamin D3 (VD3) (1.68 IU/g/week) for 16 weeks. Meanwhile, palmitic acid (PA)-induced HepG2 cells were treated with 1,25(OH)2D3 (10 nM). The general conditions of the mice were evaluated by measuring body weight, liver/body weight, serum biochemical parameters, and inflammation indices. Additionally, injury-associated indices and histopathology were used to assess the severity of liver injury. Furthermore, indicators of ferroptosis, including lipid peroxidation, iron aggregation, and the aberrant expression of related proteins, were determined using Prussian blue staining, ELISA assay, and Western blot. Results Long-term VD3 administration significantly reduced body weight gain and the liver/body weight ratio of HFD-induced MAFLD mice, while also improving serum lipid metabolism dysregulation and enhancing insulin sensitivity. The changes in the expressions of liver injury indices and histological manifestations due to VD3 treatment indicated that VD3 may exerts beneficial effects on liver injury through inhibiting inflammatory cell infiltration and vacuolation. Importantly, VD3 supplementation also inhibited ferroptosis by enhancing the body’s antioxidant capacity, reducing local iron aggregation, and modulating the expression levels of ferroptosis-related proteins. These findings were further confirmed in a PA-induced HepG2 steatosis cell model, highlighting the pharmacological effects of VD. Conclusions VD shows promise in mitigating HFD -induced liver injury by improving metabolic dysregulation and inhibiting ferroptosis, suggesting therapeutic potential in MAFLD. Graphical Abstract
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Keywords {🔍}
pubmed, article, google, scholar, cas, liver, disease, vitamin, central, fatty, metabolic, ferroptosis, nonalcoholic, wang, zhang, cell, httpsdoiorgs, supplementation, mice, lipid, mol, biol, pathway, liu, mafld, iron, expression, effects, sci, med, hepatic, data, chen, metabolism, access, front, content, miao, jiang, role, stress, privacy, cookies, journal, alleviates, inhibiting, yufan, xing, mechanisms, cells,
Topics {✒️}
mt2/camp/pka/ire1 signaling pathway month download article/chapter methionine choline-deficient diet retrospective cross-section research liver/body weight ratio high-fat diet prevent hydroperoxide-induced ferroptosis nf-κb-hepcidin axis peroxisome proliferator-activated receptors induced hepatic fibrosis nonclassical estrogen receptor/liver male c57bl/6j mice hfd-induced mafld mice article european journal db/db mice fed pancreatic β-cell function liver/body weight full article pdf fatty liver disease induced hepg2 cells inhibits tamoxifen-induced randomized clinical trial regulating keap1-nrf2-gpx4 measuring body weight improving metabolic dysregulation fat-1 transgenic mice improves metabolic disorders supplementation alleviates initiation steatotic liver disease privacy choices/manage cookies liver fibrogenic factors coronary heart disease inflammatory bowel disease high-dose vitamin european economic area serum biochemical parameters liver fibrogenic micrornas autoimmune rheumatic diseases zebrafish liver cells improve liver enzymes accepted manuscript version article miao mitochondrial contact site hypothalamic obese rats inhibiting ferroptosis pathway holds exclusive rights ferroptosis-related proteins randomized controlled trials rock/ampk pathway examine iron distribution
Questions {❓}
- Feng G, Byrne CD, Targher G, Wang F, Zheng MH (2022) Ferroptosis and metabolic dysfunction-associated fatty liver disease: is there a link?
- Gofton C, Upendran Y, Zheng MH, George J (2023) MAFLD: how is it different from NAFLD?
- Keane JT, Elangovan H, Stokes RA, Gunton JE (2018) Vitamin D and the liver-correlation or cause?
- Sharifi N, Amani R, Hajiani E et al (2014) Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease?
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headline:Vitamin D supplementation alleviates high fat diet-induced metabolic associated fatty liver disease by inhibiting ferroptosis pathway
description:Recently, a significant negative correlation has been found between vitamin D (VD) and metabolic associated fatty liver disease (MAFLD), suggesting a potential beneficial role of VD in preventing of MAFLD, while underscoring the importance of exploring its mechanisms. The experiment comprised two parts: male C57BL/6J mice (6 weeks) were fed a high-fat diet (HFD) and intraperitoneally injected with vitamin D3 (VD3) (1.68 IU/g/week) for 16 weeks. Meanwhile, palmitic acid (PA)-induced HepG2 cells were treated with 1,25(OH)2D3 (10 nM). The general conditions of the mice were evaluated by measuring body weight, liver/body weight, serum biochemical parameters, and inflammation indices. Additionally, injury-associated indices and histopathology were used to assess the severity of liver injury. Furthermore, indicators of ferroptosis, including lipid peroxidation, iron aggregation, and the aberrant expression of related proteins, were determined using Prussian blue staining, ELISA assay, and Western blot. Long-term VD3 administration significantly reduced body weight gain and the liver/body weight ratio of HFD-induced MAFLD mice, while also improving serum lipid metabolism dysregulation and enhancing insulin sensitivity. The changes in the expressions of liver injury indices and histological manifestations due to VD3 treatment indicated that VD3 may exerts beneficial effects on liver injury through inhibiting inflammatory cell infiltration and vacuolation. Importantly, VD3 supplementation also inhibited ferroptosis by enhancing the body’s antioxidant capacity, reducing local iron aggregation, and modulating the expression levels of ferroptosis-related proteins. These findings were further confirmed in a PA-induced HepG2 steatosis cell model, highlighting the pharmacological effects of VD. VD shows promise in mitigating HFD -induced liver injury by improving metabolic dysregulation and inhibiting ferroptosis, suggesting therapeutic potential in MAFLD.
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description:Recently, a significant negative correlation has been found between vitamin D (VD) and metabolic associated fatty liver disease (MAFLD), suggesting a potential beneficial role of VD in preventing of MAFLD, while underscoring the importance of exploring its mechanisms. The experiment comprised two parts: male C57BL/6J mice (6 weeks) were fed a high-fat diet (HFD) and intraperitoneally injected with vitamin D3 (VD3) (1.68 IU/g/week) for 16 weeks. Meanwhile, palmitic acid (PA)-induced HepG2 cells were treated with 1,25(OH)2D3 (10 nM). The general conditions of the mice were evaluated by measuring body weight, liver/body weight, serum biochemical parameters, and inflammation indices. Additionally, injury-associated indices and histopathology were used to assess the severity of liver injury. Furthermore, indicators of ferroptosis, including lipid peroxidation, iron aggregation, and the aberrant expression of related proteins, were determined using Prussian blue staining, ELISA assay, and Western blot. Long-term VD3 administration significantly reduced body weight gain and the liver/body weight ratio of HFD-induced MAFLD mice, while also improving serum lipid metabolism dysregulation and enhancing insulin sensitivity. The changes in the expressions of liver injury indices and histological manifestations due to VD3 treatment indicated that VD3 may exerts beneficial effects on liver injury through inhibiting inflammatory cell infiltration and vacuolation. Importantly, VD3 supplementation also inhibited ferroptosis by enhancing the body’s antioxidant capacity, reducing local iron aggregation, and modulating the expression levels of ferroptosis-related proteins. These findings were further confirmed in a PA-induced HepG2 steatosis cell model, highlighting the pharmacological effects of VD. VD shows promise in mitigating HFD -induced liver injury by improving metabolic dysregulation and inhibiting ferroptosis, suggesting therapeutic potential in MAFLD.
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High fatty diet
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