Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism.
Fatty acid metabolism
Glucose metabolism
Insulin resistance
Kinase signaling
Peroxisome
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
12
03
2022
revised:
04
05
2022
accepted:
05
05
2022
pubmed:
14
5
2022
medline:
7
7
2022
entrez:
13
5
2022
Statut:
ppublish
Résumé
The liver is the primary internal metabolic organ that coordinates whole body energy homeostasis in response to feeding and fasting. Genetic ablation or pharmacological inhibition of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) has been shown to significantly improve hepatic health and peripheral insulin sensitivity upon overnutrition with high fat diet. However, the precise molecular underpinnings that explain this metabolic protection have remained largely undefined. To characterize the role of CaMKK2 in hepatic metabolism, we developed and challenged liver-specific CaMKK2 knockout (CaMKK2 Consistent with previous findings, we show that hepatic CaMKK2 ablation significantly improves indices of peripheral insulin sensitivity. Mechanistically, we found that CaMKK2 phosphorylates and regulates GAPDH to promote glucose metabolism and PEX3 to blunt peroxisomal fatty acid catabolism in the liver. CaMKK2 is a central metabolic fuel sensor in the liver that significantly contributes to whole body systems metabolism.
Identifiants
pubmed: 35562082
pii: S2212-8778(22)00082-5
doi: 10.1016/j.molmet.2022.101513
pmc: PMC9157561
pii:
doi:
Substances chimiques
Fatty Acids
0
Calcium-Calmodulin-Dependent Protein Kinase Kinase
EC 2.7.11.17
Camkk2 protein, mouse
EC 2.7.11.17
Glucose
IY9XDZ35W2
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
101513Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006348
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114356
Pays : United States
Organisme : NIH HHS
ID : S10 OD012304
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM056929
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.
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