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Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control
Considerable evidence confirms the importance of Cyp26a1 to all-trans-retinoic acid (RA) homeostasis during embryogenesis. In contrast, despite its presence in postnatal liver as a potential major RA catabolizing enzyme and its acute sensitivity to induction by RA, some data suggested that Cyp26a1 c...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176252/ https://www.ncbi.nlm.nih.gov/pubmed/37011860 http://dx.doi.org/10.1016/j.jbc.2023.104669 |
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author | Yoo, Hong Sik Cockrum, Michael A. Napoli, Joseph L. |
author_facet | Yoo, Hong Sik Cockrum, Michael A. Napoli, Joseph L. |
author_sort | Yoo, Hong Sik |
collection | PubMed |
description | Considerable evidence confirms the importance of Cyp26a1 to all-trans-retinoic acid (RA) homeostasis during embryogenesis. In contrast, despite its presence in postnatal liver as a potential major RA catabolizing enzyme and its acute sensitivity to induction by RA, some data suggested that Cyp26a1 contributes only marginally to endogenous RA homeostasis postnatally. We report reevaluation of a conditional Cyp26a1 knockdown in the postnatal mouse. The current results show that Cyp26a1 mRNA in WT mouse liver increases 16-fold upon refeeding after a fast, accompanied by an increased rate of RA elimination and a 41% decrease in the RA concentration. In contrast, Cyp26a1 mRNA in the refed homozygotic knockdown reached only 2% of its extent in WT during refeeding, accompanied by a slower rate of RA catabolism and no decrease in liver RA, relative to fasting. Refed homozygous knockdown mice also had decreased Akt1 and 2 phosphorylation and pyruvate dehydrogenase kinase 4 (Pdk4) mRNA and increased glucokinase (Gck) mRNA, glycogen phosphorylase (Pygl) phosphorylation, and serum glucose, relative to WT. Fasted homozygous knockdown mice had increased glucagon/insulin relative to WT. These data indicate that Cyp26a1 participates prominently in moderating the postnatal liver concentration of endogenous RA and contributes essentially to glucoregulatory control. |
format | Online Article Text |
id | pubmed-10176252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-101762522023-05-13 Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control Yoo, Hong Sik Cockrum, Michael A. Napoli, Joseph L. J Biol Chem Research Article Collection: Metabolism Considerable evidence confirms the importance of Cyp26a1 to all-trans-retinoic acid (RA) homeostasis during embryogenesis. In contrast, despite its presence in postnatal liver as a potential major RA catabolizing enzyme and its acute sensitivity to induction by RA, some data suggested that Cyp26a1 contributes only marginally to endogenous RA homeostasis postnatally. We report reevaluation of a conditional Cyp26a1 knockdown in the postnatal mouse. The current results show that Cyp26a1 mRNA in WT mouse liver increases 16-fold upon refeeding after a fast, accompanied by an increased rate of RA elimination and a 41% decrease in the RA concentration. In contrast, Cyp26a1 mRNA in the refed homozygotic knockdown reached only 2% of its extent in WT during refeeding, accompanied by a slower rate of RA catabolism and no decrease in liver RA, relative to fasting. Refed homozygous knockdown mice also had decreased Akt1 and 2 phosphorylation and pyruvate dehydrogenase kinase 4 (Pdk4) mRNA and increased glucokinase (Gck) mRNA, glycogen phosphorylase (Pygl) phosphorylation, and serum glucose, relative to WT. Fasted homozygous knockdown mice had increased glucagon/insulin relative to WT. These data indicate that Cyp26a1 participates prominently in moderating the postnatal liver concentration of endogenous RA and contributes essentially to glucoregulatory control. American Society for Biochemistry and Molecular Biology 2023-04-01 /pmc/articles/PMC10176252/ /pubmed/37011860 http://dx.doi.org/10.1016/j.jbc.2023.104669 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Collection: Metabolism Yoo, Hong Sik Cockrum, Michael A. Napoli, Joseph L. Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
title | Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
title_full | Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
title_fullStr | Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
title_full_unstemmed | Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
title_short | Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
title_sort | cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control |
topic | Research Article Collection: Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176252/ https://www.ncbi.nlm.nih.gov/pubmed/37011860 http://dx.doi.org/10.1016/j.jbc.2023.104669 |
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