Resveratrol Induces the Fasting State and Alters Circadian Metabolism in Hepatocytes.
Circadian
Clock
Gluconeogenesis
Liver
Metabolism
PP2A
Resveratrol
Journal
Plant foods for human nutrition (Dordrecht, Netherlands)
ISSN: 1573-9104
Titre abrégé: Plant Foods Hum Nutr
Pays: Netherlands
ID NLM: 8803554
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
accepted:
03
02
2022
pubmed:
19
2
2022
medline:
13
4
2022
entrez:
18
2
2022
Statut:
ppublish
Résumé
Resveratrol is a nutritional substance that has both metabolic and circadian effects. While some studies indicate a correlation between resveratrol and reduced gluconeogenesis, others propose the opposite. Our aim was to study the metabolic effect of resveratrol around the circadian clock in order to determine more accurately the hepatic signaling pathways involved. AML-12 hepatocytes were treated with resveratrol and clock and metabolic markers were measured around the clock. Resveratrol-treated AML-12 hepatocytes showed reduced ratio of the following key metabolic factors: phosphorylated PP2A to total PP2A (pPP2A/PP2A), pAKT/AKT, pFOXO1/FOXO1 and pAMPK/AMPK, indicating inhibition of AKT and AMPK, but activation of PP2A and FOXO1. In addition, the levels of phosphorylated mTOR were low after resveratrol treatment. The levels of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were significantly higher after resveratrol treatment. In accordance with the reduced mTOR activity, the ratio of pBMAL1/BMAL1, the clock transcription factor, also decreased. Bmal1 mRNA oscillated robustly in AML-12 hepatocytes, but resveratrol treatment led to a phase advance and a decrease in its amplitude, similarly to the effect on Srebp1c and Pgc1α mRNA. After resveratrol treatment, daily mRNA levels of Bmal1, Sirt1 and Srebp1c were significantly higher. Resveratrol changes the circadian expression of metabolic and clock genes activating the fasting state and inducing the PP2A-FOXO1-PEPCK pathway.
Identifiants
pubmed: 35178649
doi: 10.1007/s11130-022-00954-7
pii: 10.1007/s11130-022-00954-7
doi:
Substances chimiques
ARNTL Transcription Factors
0
RNA, Messenger
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Resveratrol
Q369O8926L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
128-134Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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