Hepatic DKK1-driven steatosis is CD36 dependent.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
11
08
2022
revised:
27
10
2022
accepted:
27
10
2022
entrez:
21
11
2022
pubmed:
22
11
2022
medline:
24
11
2022
Statut:
epublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide; about 25% of NAFLD silently progress into steatohepatitis, in which some of them may develop into fibrosis, cirrhosis and liver failure. However, few drugs are available for NAFLD, partly because of an incomplete understanding of its pathogenic mechanisms. Here, using in vivo and in vitro gain- and loss-of-function approaches, we identified up-regulated DKK1 plays a pivotal role in high-fat diet-induced NAFLD and its progression. Mechanistic analysis reveals that DKK1 enhances the capacity of hepatocytes to uptake fatty acids through the ERK-PPARγ-CD36 axis. Moreover, DKK1 increased insulin resistance by activating the JNK signaling, which in turn exacerbates disorders of hepatic lipid metabolism. Our finding suggests that DKK1 may be a potential therapeutic and diagnosis candidate for NAFLD and metabolic disorder progression.
Identifiants
pubmed: 36410795
pii: 6/1/e202201665
doi: 10.26508/lsa.202201665
pmc: PMC9679335
pii:
doi:
Substances chimiques
DKK1 protein, human
0
Intercellular Signaling Peptides and Proteins
0
CD36 Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIEHS NIH HHS
ID : 27302C0031
Pays : United States
Informations de copyright
© 2022 Yang et al.
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