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Paricalcitol attenuates oxidative stress and inflammatory response in the liver of NAFLD rats by regulating FOXO3a and NFκB acetylation.
- Source :
-
Cellular signalling [Cell Signal] 2024 Sep; Vol. 121, pp. 111299. Date of Electronic Publication: 2024 Jul 14. - Publication Year :
- 2024
-
Abstract
- The lack of therapeutics along with complex pathophysiology made non-alcoholic fatty liver disease (NAFLD) a research hotspot. Studies showed that the deficiency of Vitamin D plays a vital role in NAFLD pathogenesis. While several research studies focused on vitamin D supplementation in NAFLD, there is still a need to understand the regulatory mechanism of direct vitamin D receptor activation in NAFLD. In the present study, we explored the role of direct Vitamin D receptor activation using paricalcitol in choline-deficient high-fat diet-induced NAFLD rat liver and its modulation on protein acetylation. Our results showed that paricalcitol administration significantly reduced the fat accumulation in HepG2 cells and the liver of NAFLD rats. Paricalcitol attenuated the elevated serum level of alanine transaminase, aspartate transaminase, insulin, low-density lipoprotein, triglyceride, and increased high-density lipoprotein in NAFLD rats. Paricalcitol significantly decreased the increased total protein acetylation by enhancing the SIRT1 and SIRT3 expression in NAFLD liver. Further, the study revealed that paricalcitol reduced the acetylation of NFκB and FOXO3a in NAFLD liver along with a decrease in the mRNA expression of IL1β, NFκB, TNFα, and increased catalase and MnSOD. Moreover, total antioxidant activity, glutathione, and catalase were also elevated, whereas lipid peroxidation, myeloperoxidase, and reactive oxygen species levels were significantly decreased in the liver of NAFLD after paricalcitol administration. The study concludes that the downregulation of SIRT1 and SIRT3 in NAFLD liver was associated with an increased acetylated NFκB and FOXO3a. Paricalcitol effectively reversed hepatic inflammation and oxidative stress in NAFLD rats through transcriptional regulation of NFκB and FOXO3a, respectively, by inhibiting their acetylation.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Acetylation drug effects
Humans
Male
Rats
Hep G2 Cells
Inflammation metabolism
Sirtuin 1 metabolism
Diet, High-Fat adverse effects
Rats, Sprague-Dawley
Sirtuins
Non-alcoholic Fatty Liver Disease metabolism
Non-alcoholic Fatty Liver Disease drug therapy
Oxidative Stress drug effects
Forkhead Box Protein O3 metabolism
Forkhead Box Protein O3 genetics
NF-kappa B metabolism
Ergocalciferols pharmacology
Ergocalciferols therapeutic use
Liver metabolism
Liver drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3913
- Volume :
- 121
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 39004324
- Full Text :
- https://doi.org/10.1016/j.cellsig.2024.111299