Novel targets of β-TrCP cooperatively accelerate carbohydrate and fatty acid consumption.
E3 ligase
energy homeostasis
metabolism
obesity
ubiquitination
β-TrCP
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
16 Aug 2023
16 Aug 2023
Historique:
revised:
29
06
2023
received:
10
03
2023
accepted:
25
07
2023
medline:
16
8
2023
pubmed:
16
8
2023
entrez:
16
8
2023
Statut:
aheadofprint
Résumé
Cellular energy is primarily produced from glucose and fat through glycolysis and fatty acid oxidation (FAO) followed by the tricarboxylic acid cycle in mitochondria; energy homeostasis is carefully maintained via numerous feedback pathways. In this report, we uncovered a new master regulator of carbohydrate and lipid metabolism. When ubiquitin E3 ligase β-TrCP2 was inducibly knocked out in β-TrCP1 knockout adult mice, the resulting double knockout mice (DKO) lost fat mass rapidly. Biochemical analyses of the tissues and cells from β-TrCP2 KO and DKO mice revealed that glycolysis, FAO, and lipolysis were dramatically upregulated. The absence of β-TrCP2 increased the protein stability of metabolic rate-limiting enzymes including 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1A (CPT1A), and carnitine/acylcarnitine translocase (CACT). Our data suggest that β-TrCP is a potential regulator for total energy homeostasis by simultaneously controlling glucose and fatty acid metabolism and that targeting β-TrCP could be an effective strategy to treat obesity and other metabolic disorders.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM131283
Pays : United States
Informations de copyright
© 2023 Wiley Periodicals LLC.
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