Systemic depletion of WWP1 improves insulin sensitivity and lowers triglyceride content in the liver of obese mice.
WWP1
adipose tissue
hepatic steatosis
obesity
Journal
FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
20
03
2023
received:
19
10
2022
accepted:
07
04
2023
medline:
6
6
2023
pubmed:
10
4
2023
entrez:
9
4
2023
Statut:
ppublish
Résumé
Obesity is a metabolic disorder associated with many diseases. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a HECT-type E3 ubiquitin ligase involved in several diseases. Recently, we found that the level of WWP1 is increased in white adipose tissue in a mouse model of obesity and that obese Wwp1 knockout (KO) mice exhibit improved whole-body glucose metabolism. Here, to determine which insulin-sensitive tissues contribute to this phenotype, we investigated the levels of several insulin signaling markers in white adipose tissue, liver, and skeletal muscle of Wwp1 KO mice, which were fed a normal or high-fat diet and transiently treated with insulin. In obese Wwp1 KO mice, phosphorylated Akt levels were increased in the liver but not in white adipose tissue or skeletal muscle. Moreover, the weight and triglyceride content of the liver of obese Wwp1 KO mice were decreased. These results suggest that systemic deletion of WWP1 improves glucose metabolism via enhanced hepatic insulin signaling and suppressed hepatic fat accumulation. In summary, WWP1 participates in obesity-related metabolic dysfunction and pathologies related to hepatic steatosis via suppressed insulin signaling.
Identifiants
pubmed: 37032433
doi: 10.1002/2211-5463.13610
pmc: PMC10240335
doi:
Substances chimiques
Triglycerides
0
Insulin
0
Glucose
IY9XDZ35W2
WWP1 protein, mouse
EC 2.3.2.26
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1086-1094Informations de copyright
© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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