Specific Compounds Derived from Traditional Chinese Medicine Ameliorate Lipid-Induced Contractile Dysfunction in Cardiomyocytes
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Published:2024-07-25
Issue:15
Volume:25
Page:8131
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Wang Fang12ORCID, Neumann Dietbert23ORCID, Kapsokalyvas Dimitris14ORCID, Hoes Martijn F.256ORCID, Schianchi Francesco1, Glatz Jan F. C.6ORCID, Nabben Miranda1256ORCID, Luiken Joost J. F. P.16
Affiliation:
1. Department of Genetics & Cell Biology, Maastricht University, 6229 ER Maastricht, The Netherlands 2. Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine and Life Science, Maastricht University, 6229 ER Maastricht, The Netherlands 3. Department of Pathology, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands 4. Interdisciplinary Centre for Clinical Research IZKF, University Hospital RWTH Aachen, 52074 Aachen, Germany 5. Department of Cardiology, Maastricht University, 6229 ER Maastricht, The Netherlands 6. Department of Clinical Genetics, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands
Abstract
Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds—Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin—derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related SIRT3 expression, and others reduced inflammatory TNFα expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.
Funder
China Scholarship Council Dutch Heart Foundation
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