Your browser doesn't support javascript.
loading
Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control.
Yoo, Hong Sik; Cockrum, Michael A; Napoli, Joseph L.
Affiliation
  • Yoo HS; Graduate Program in Metabolic Biology, Nutritional Sciences and Toxicology, UC-Berkeley, Berkeley, California, USA.
  • Cockrum MA; Graduate Program in Metabolic Biology, Nutritional Sciences and Toxicology, UC-Berkeley, Berkeley, California, USA.
  • Napoli JL; Graduate Program in Metabolic Biology, Nutritional Sciences and Toxicology, UC-Berkeley, Berkeley, California, USA. Electronic address: jna@berkeley.edu.
J Biol Chem ; 299(5): 104669, 2023 05.
Article de En | MEDLINE | ID: mdl-37011860
ABSTRACT
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.
Sujet(s)
Mots clés

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Trétinoïne / Glycémie / Retinoic acid 4-hydroxylase / Homéostasie Limites: Animals Langue: En Journal: J Biol Chem Année: 2023 Type de document: Article Pays d'affiliation: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Trétinoïne / Glycémie / Retinoic acid 4-hydroxylase / Homéostasie Limites: Animals Langue: En Journal: J Biol Chem Année: 2023 Type de document: Article Pays d'affiliation: États-Unis d'Amérique