Fatty acid binding protein 4 (FABP4) as a potential biomarker reflecting myocardial lipid storage in type 2 diabetes.
Animals
Biomarkers
/ blood
Biphenyl Compounds
/ therapeutic use
Cell Line
Diabetes Mellitus, Type 2
/ blood
Diabetic Cardiomyopathies
/ blood
Diet, High-Fat
Fatty Acid-Binding Proteins
/ antagonists & inhibitors
Female
Humans
Insulin
Lipid Metabolism
Male
Mice
Mice, Inbred C57BL
Middle Aged
Myocardium
/ metabolism
Pyrazoles
/ therapeutic use
Signal Transduction
Triglycerides
/ metabolism
BMS309403
Cardiac lipotoxicity
FABP4
Insulin resistance
Myocardial neutral lipid content
Journal
Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
15
01
2019
revised:
27
03
2019
accepted:
08
04
2019
pubmed:
19
4
2019
medline:
8
2
2020
entrez:
19
4
2019
Statut:
ppublish
Résumé
Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone involved in the crosstalk between adipose and peripheral tissues, and it contributes to widespread insulin resistance in cells, including cardiac cells. However, the role of this adipokine in regulating cardiac metabolism and myocardial neutral lipid content in patients with type 2 diabetes has not been elucidated. The impact of circulating FABP4 on the cardiac neutral lipid content was measured by proton magnetic resonance spectroscopy ( Serum FABP4 levels were higher in type 2 diabetic patients compared to healthy individuals. Circulating FABP4 levels were associated with myocardial neutral lipid content in type 2 diabetic patients. In HFD-fed mice, both serum FABP4 and myocardial triglyceride content were increased. In FABP4-challenged HL-1 cells, extracellular FABP4 increased intracellular lipid accumulation, which led to impairment of the insulin-signalling pathway and reduced insulin-stimulated glucose uptake. However, these effects were partially reversed by FABP4 inhibition with BMS309403, which attenuated the intracellular lipid content and improved insulin signalling and insulin-stimulated glucose uptake. Taken together, our results identify FABP4 as a molecule involved in diabetic/lipid-induced cardiomyopathy and indicate that this molecule may be an emerging biomarker for diabetic cardiomyopathy-related disturbances, such as myocardial neutral lipid accumulation. Additionally, FABP4 inhibition may be a potential therapeutic target for metabolic-related cardiac dysfunctions.
Identifiants
pubmed: 30999003
pii: S0026-0495(19)30073-3
doi: 10.1016/j.metabol.2019.04.007
pii:
doi:
Substances chimiques
2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid
0
Biomarkers
0
Biphenyl Compounds
0
FABP4 protein, human
0
Fabp4 protein, mouse
0
Fatty Acid-Binding Proteins
0
Insulin
0
Pyrazoles
0
Triglycerides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12-21Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.