Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver.
Aldolase b
DHAP
Inflammation
Interleukin 6
Lean NAFLD
Non-alcoholic fatty liver
Journal
Biochimica et biophysica acta. Molecular and cell biology of lipids
ISSN: 1879-2618
Titre abrégé: Biochim Biophys Acta Mol Cell Biol Lipids
Pays: Netherlands
ID NLM: 101731727
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
29
09
2020
revised:
21
01
2021
accepted:
09
02
2021
pubmed:
15
2
2021
medline:
30
6
2021
entrez:
14
2
2021
Statut:
ppublish
Résumé
Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD), although their relationship is unclear. In a transgenic zebrafish system with chronic systemic overexpression of human IL6 (IL6-OE) we show that inflammation can cause intra-hepatic accumulation of triglycerides. Transcriptomics and proteomics analysis of the IL6-OE liver revealed a deregulation of glycolysis/gluconeogenesis pathway, especially a striking down regulation of the glycolytic enzyme aldolase b. Metabolomics analysis by mass spectrometry showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for fatty liver. This mechanism may be relevant for NAFLD in lean individuals, an emerging class of NAFLD prevalent more in Asian Indian populations.
Identifiants
pubmed: 33582286
pii: S1388-1981(21)00031-7
doi: 10.1016/j.bbalip.2021.158905
pii:
doi:
Substances chimiques
IL6 protein, human
0
Interleukin-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158905Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.