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Erschienen in: Current Hypertension Reports 6/2012

01.12.2012 | Mediators, Mechanisms, and Pathways in Tissue Injury (B Rothermel, Section Editor)

Mechanisms of Lipotoxicity in the Cardiovascular System

verfasst von: Adam R. Wende, J. David Symons, E. Dale Abel

Erschienen in: Current Hypertension Reports | Ausgabe 6/2012

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Abstract

Cardiovascular diseases account for approximately one third of all deaths globally. Obese and diabetic patients have a high likelihood of dying from complications associated with cardiovascular dysfunction. Obesity and diabetes increase circulating lipids that upon tissue uptake, may be stored as triglyceride, or may be metabolized in other pathways, leading to the generation of toxic intermediates. Excess lipid utilization or activation of signaling pathways by lipid metabolites may disrupt cellular homeostasis and contribute to cell death, defining the concept of lipotoxicity. Lipotoxicity occurs in multiple organs, including cardiac and vascular tissues, and a number of specific mechanisms have been proposed to explain lipotoxic tissue injury. In addition, recent data suggests that increased tissue lipids may also be protective in certain contexts. This review will highlight recent progress toward elucidating the relationship between nutrient oversupply, lipotoxicity, and cardiovascular dysfunction. The review will focus in two sections on the vasculature and cardiomyocytes respectively.
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68.
Zurück zum Zitat Bikman BT, Guan Y, Shui G, et al. Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. J Biol Chem. 2012;287:17426–37.PubMedCrossRef Bikman BT, Guan Y, Shui G, et al. Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis. J Biol Chem. 2012;287:17426–37.PubMedCrossRef
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Zurück zum Zitat Liu L, Yu S, Khan RS, et al. DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle. J Lipid Res. 2011;52:732–44.PubMedCrossRef Liu L, Yu S, Khan RS, et al. DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle. J Lipid Res. 2011;52:732–44.PubMedCrossRef
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Zurück zum Zitat Mitra R, Nogee DP, Zechner JF, et al. The transcriptional coactivators, PGC-1α and beta, cooperate to maintain cardiac mitochondrial function during the early stages of insulin resistance. J Mol Cell Cardiol. 2012;52:701–10.PubMedCrossRef Mitra R, Nogee DP, Zechner JF, et al. The transcriptional coactivators, PGC-1α and beta, cooperate to maintain cardiac mitochondrial function during the early stages of insulin resistance. J Mol Cell Cardiol. 2012;52:701–10.PubMedCrossRef
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Zurück zum Zitat Nakamura H, Matoba S, Iwai-Kanai E, et al. p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation / clinical perspective. Circulation: Heart Failure. 2012;5:106–15.CrossRef Nakamura H, Matoba S, Iwai-Kanai E, et al. p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation / clinical perspective. Circulation: Heart Failure. 2012;5:106–15.CrossRef
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Zurück zum Zitat •• Shimizu I, Yoshida Y, Katsuno T, et al. p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab. 2012;15:51–64. Findings in this study revealed important cross talk between adipose and cardiac tissue in response to pressure overload. Specifically, regulation of lipolysis by p53 enhances inflammation and leads to the development of insulin resistance.PubMedCrossRef •• Shimizu I, Yoshida Y, Katsuno T, et al. p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab. 2012;15:51–64. Findings in this study revealed important cross talk between adipose and cardiac tissue in response to pressure overload. Specifically, regulation of lipolysis by p53 enhances inflammation and leads to the development of insulin resistance.PubMedCrossRef
81.
Zurück zum Zitat •• Grueter CE, van Rooij E, Johnson BA, et al. A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell. 2012;149:671–83. This study revealed that a cardiac-restricted microRNA specifically regulates peripheral metabolic homeostasis. The specific cardiac mediator of this effect remains to be identified..PubMedCrossRef •• Grueter CE, van Rooij E, Johnson BA, et al. A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell. 2012;149:671–83. This study revealed that a cardiac-restricted microRNA specifically regulates peripheral metabolic homeostasis. The specific cardiac mediator of this effect remains to be identified..PubMedCrossRef
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Zurück zum Zitat Zhang L, Ussher JR, Oka T, et al. Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation. Cardiovasc Res. 2011;89:148–56.PubMedCrossRef Zhang L, Ussher JR, Oka T, et al. Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation. Cardiovasc Res. 2011;89:148–56.PubMedCrossRef
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Zurück zum Zitat Sharma V, Sharma A, Saran V, et al. beta-receptor antagonist treatment prevents activation of cell death signaling in the diabetic heart independent of its metabolic actions. Eur J Pharmacol. 2011;657:117–25.PubMedCrossRef Sharma V, Sharma A, Saran V, et al. beta-receptor antagonist treatment prevents activation of cell death signaling in the diabetic heart independent of its metabolic actions. Eur J Pharmacol. 2011;657:117–25.PubMedCrossRef
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Zurück zum Zitat • Battiprolu PK, Hojayev B, Jiang N, et al. Metabolic stress-induced activation of FOXO1 triggers diabetic cardiomyopathy in mice. J Clin Invest. 2012;122:1109–18. The data presented in this manuscript directly links HFD induced transcriptional changes via the forkhead transcription factor FOXO1 to cardiac dysfunction and lipotoxic cardiomyopathy in a model of severe diet-induced obesity acting in part via decreased IRS-1 mediated Akt-signaling.PubMedCrossRef • Battiprolu PK, Hojayev B, Jiang N, et al. Metabolic stress-induced activation of FOXO1 triggers diabetic cardiomyopathy in mice. J Clin Invest. 2012;122:1109–18. The data presented in this manuscript directly links HFD induced transcriptional changes via the forkhead transcription factor FOXO1 to cardiac dysfunction and lipotoxic cardiomyopathy in a model of severe diet-induced obesity acting in part via decreased IRS-1 mediated Akt-signaling.PubMedCrossRef
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Zurück zum Zitat Ferland-McCollough D, Fernandez-Twinn DS, Cannell IG, et al. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death Differ. 2012;19:1003–12.PubMedCrossRef Ferland-McCollough D, Fernandez-Twinn DS, Cannell IG, et al. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death Differ. 2012;19:1003–12.PubMedCrossRef
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Zurück zum Zitat Pulakat L, Aroor AR, Gul R, Sowers JR: Cardiac insulin resistance and microRNA modulators. Exp Diabetes Res 2012, In press. Pulakat L, Aroor AR, Gul R, Sowers JR: Cardiac insulin resistance and microRNA modulators. Exp Diabetes Res 2012, In press.
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Zurück zum Zitat Sacco J, Adeli K. MicroRNAs: Emerging roles in lipid and lipoprotein metabolism. Curr Opin Lipidol. 2012;23:220–5.PubMedCrossRef Sacco J, Adeli K. MicroRNAs: Emerging roles in lipid and lipoprotein metabolism. Curr Opin Lipidol. 2012;23:220–5.PubMedCrossRef
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Zurück zum Zitat Alfaradhi MZ, Ozanne SE. Developmental programming in response to maternal overnutrition. Front Genet. 2011;2:1–12. Alfaradhi MZ, Ozanne SE. Developmental programming in response to maternal overnutrition. Front Genet. 2011;2:1–12.
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Zurück zum Zitat Marsh SA, Powell PC, Dell'italia LJ, Chatham JC. Cardiac O-GlcNAcylation blunts autophagic signaling in the diabetic heart. Life Sci 2012, In press. Marsh SA, Powell PC, Dell'italia LJ, Chatham JC. Cardiac O-GlcNAcylation blunts autophagic signaling in the diabetic heart. Life Sci 2012, In press.
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Metadaten
Titel
Mechanisms of Lipotoxicity in the Cardiovascular System
verfasst von
Adam R. Wende
J. David Symons
E. Dale Abel
Publikationsdatum
01.12.2012
Verlag
Current Science Inc.
Erschienen in
Current Hypertension Reports / Ausgabe 6/2012
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-012-0307-2

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