Docosahexaenoic Acid Modulates Nonalcoholic Fatty Liver Disease by Suppressing Endocannabinoid System

© 2024 Wiley‐VCH GmbH..

SCOPE: Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system.

METHODS AND RESULTS: In a case-control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high-fat and -cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2-arachidoniylglycerol (2-AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2-AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0-ceramide contents, resulting in down-regulation of de novo fatty acid synthesis and up-regulation of fatty acid β-oxidation related protein expression levels.

CONCLUSIONS: This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:68

Enthalten in:

Molecular nutrition & food research - 68(2024), 7 vom: 15. Apr., Seite e2300616

Sprache:

Englisch

Beteiligte Personen:

Chen, Yan-Fang [VerfasserIn]
Fan, Ze-Kai [VerfasserIn]
Wang, Yin-Peng [VerfasserIn]
Liu, Peng [VerfasserIn]
Guo, Xiao-Fei [VerfasserIn]
Li, Duo [VerfasserIn]

Links:

Volltext

Themen:

25167-62-8
AAN7QOV9EA
Adiponectin
Ceramides
Docosahexaenoic Acids
Docosahexaenoic acid
Eicosapentaenoic Acid
Eicosapentaenoic acid
Endocannabinoid system
Endocannabinoids
Journal Article
Nonalcoholic fatty liver disease

Anmerkungen:

Date Completed 17.04.2024

Date Revised 17.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/mnfr.202300616

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369200896