Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study

Abstract Background Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research expl...

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Autores principales:	Dan-meng Zheng, Zhen-ni An, Ming-hao Ge, Dong-zhuo Wei, Ding-wen Jiang, Xue-jiao Xing, Xiao-lei Shen, Chang Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Diabetic cardiomyopathy Metabolomics Acylcarnitine Lipid metabolism AMPK Nutritional diseases. Deficiency diseases RC620-627
Acceso en línea:	https://doaj.org/article/de6d745a5e144dc58dc7c552f20e049e
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spelling	oai:doaj.org-article:de6d745a5e144dc58dc7c552f20e049e2021-11-08T11:16:04ZMedium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study10.1186/s12944-021-01576-91476-511Xhttps://doaj.org/article/de6d745a5e144dc58dc7c552f20e049e2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12944-021-01576-9https://doaj.org/toc/1476-511XAbstract Background Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. Methods In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. Results Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. Conclusions The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.Dan-meng ZhengZhen-ni AnMing-hao GeDong-zhuo WeiDing-wen JiangXue-jiao XingXiao-lei ShenChang LiuBMCarticleDiabetic cardiomyopathyMetabolomicsAcylcarnitineLipid metabolismAMPKNutritional diseases. Deficiency diseasesRC620-627ENLipids in Health and Disease, Vol 20, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diabetic cardiomyopathy Metabolomics Acylcarnitine Lipid metabolism AMPK Nutritional diseases. Deficiency diseases RC620-627
spellingShingle	Diabetic cardiomyopathy Metabolomics Acylcarnitine Lipid metabolism AMPK Nutritional diseases. Deficiency diseases RC620-627 Dan-meng Zheng Zhen-ni An Ming-hao Ge Dong-zhuo Wei Ding-wen Jiang Xue-jiao Xing Xiao-lei Shen Chang Liu Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
description	Abstract Background Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. Methods In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. Results Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. Conclusions The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.
format	article
author	Dan-meng Zheng Zhen-ni An Ming-hao Ge Dong-zhuo Wei Ding-wen Jiang Xue-jiao Xing Xiao-lei Shen Chang Liu
author_facet	Dan-meng Zheng Zhen-ni An Ming-hao Ge Dong-zhuo Wei Ding-wen Jiang Xue-jiao Xing Xiao-lei Shen Chang Liu
author_sort	Dan-meng Zheng
title	Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
title_short	Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
title_full	Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
title_fullStr	Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
title_full_unstemmed	Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
title_sort	medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study
publisher	BMC
publishDate	2021
url	https://doaj.org/article/de6d745a5e144dc58dc7c552f20e049e
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Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study

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