The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease-The Transition from an Adipocentric to Liver-Centric Approach.
ER stress
NAFLD
adipose tissue
circadian clock
hepatokines
insulin resistance
lipotoxicity
low-grade inflammation
Journal
Current issues in molecular biology
ISSN: 1467-3045
Titre abrégé: Curr Issues Mol Biol
Pays: Switzerland
ID NLM: 100931761
Informations de publication
Date de publication:
14 Nov 2023
14 Nov 2023
Historique:
received:
03
10
2023
revised:
01
11
2023
accepted:
09
11
2023
medline:
24
11
2023
pubmed:
24
11
2023
entrez:
24
11
2023
Statut:
epublish
Résumé
The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.
Identifiants
pubmed: 37998747
pii: cimb45110570
doi: 10.3390/cimb45110570
pmc: PMC10670061
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
9084-9102Subventions
Organisme : Wellcome Trust
ID : 200110
Pays : United Kingdom
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