Cardiomyopathy in obesity, insulin resistance and diabetes.
PPAR
cardiomyopathy
diabetes
dyslipidemia
fatty acid
fibrate
hypertriglyceridemia
insulin resistance
lipid accumulation
lipotoxicity
obesity
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
03
01
2019
accepted:
25
02
2019
pubmed:
15
3
2019
medline:
16
2
2021
entrez:
15
3
2019
Statut:
ppublish
Résumé
The prevalence of obesity, insulin resistance and diabetes is increasing rapidly. Most patients with these disorders have hypertriglyceridaemia and increased plasma levels of fatty acids, which are taken up and stored in lipid droplets in the heart. Intramyocardial lipids that exceed the capacity for storage and oxidation can be lipotoxic and induce non-ischaemic and non-hypertensive cardiomyopathy, termed diabetic or lipotoxic cardiomyopathy. The clinical features of diabetic cardiomyopathy are cardiac hypertrophy and diastolic dysfunction, which lead to heart failure, especially heart failure with preserved ejection fraction. Although the pathogenesis of the cardiomyopathy is multifactorial, diabetic dyslipidaemia and intramyocardial lipid accumulation are the key pathological features, triggering cellular signalling and modifications of proteins and lipids via generation of toxic metabolic intermediates. Most clinical studies have shown no beneficial effect of anti-diabetic agents and statins on outcomes in heart failure patients without atherosclerotic diseases, indicating the importance of identifying underlying mechanisms and early interventions for diabetic cardiomyopathy. Here, we summarize the molecular mechanisms of diabetic cardiomyopathy, with a special emphasis on cardiac lipotoxicity, and discuss the role of peroxisome proliferator-activated receptor α and dysregulated fatty acid metabolism as potential therapeutic targets.
Substances chimiques
Hypoglycemic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2977-2993Subventions
Organisme : NIH HHS
ID : HL112330
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL091469
Pays : United States
Organisme : American Heart Association Scientist Development
ID : 17SDG33660358
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL144626
Pays : United States
Organisme : NIH HHS
ID : HL138720
Pays : United States
Organisme : NIH HHS
ID : S10 OD025238
Pays : United States
Organisme : NIH HHS
ID : AG023039
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL112330
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL150881
Pays : United States
Organisme : Foundation Leducq Transatlantic Network of Excellence
ID : 15CBD04
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL138720
Pays : United States
Organisme : NIH HHS
ID : HL067724
Pays : United States
Organisme : NIH HHS
ID : HL091469
Pays : United States
Informations de copyright
© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.
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