Endogenous triacylglycerol metabolism in diabetic heart

Paulson, Dennis J.; Crass, M. F.

doi:10.1152/ajpheart.1982.242.6.h1084

Cited by 64 publications

(58 citation statements)

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“…Cardiac myocyte lipid accumulation may also contribute to the pathogenesis of diabetic cardiomyopathy. In animal models of diabetes, 2-to 3.7-fold increases in myocyte triglyceride have been reported (20,34,35). Similarly, in obese Zucker diabetic fatty (ZDF) rats there is threefold increase in triglyceride accumulation, which is associated with cardiac dilatation and a small but significant reduction in leftventricular contractility (18).…”

Section: Discussionmentioning

confidence: 98%

A novel mouse model of lipotoxic cardiomyopathy

Chiu

Kovács²,

Ford³

et al. 2001

J. Clin. Invest.

690

562

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Inherited and acquired cardiomyopathies are associated with marked intracellular lipid accumulation in the heart. To test the hypothesis that mismatch between myocardial fatty acid uptake and utilization leads to the accumulation of cardiotoxic lipid species, and to establish a mouse model of metabolic cardiomyopathy, we generated transgenic mouse lines that overexpress long-chain acylCoA synthetase in the heart (MHC-ACS). This protein plays an important role in vectorial fatty acid transport across the plasma membrane. MHC-ACS mice demonstrate cardiac-restricted expression of the transgene and marked cardiac myocyte triglyceride accumulation. Lipid accumulation is associated with initial cardiac hypertrophy, followed by the development of left-ventricular dysfunction and premature death. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and cytochrome c release in transgenic hearts suggest that cardiac myocyte death occurs, in part, by lipid-induced programmed cell death. Taken together, our data demonstrate that fatty acid uptake/utilization mismatch in the heart leads to accumulation of lipid species toxic to cardiac myocytes. This novel mouse model will provide insight into the role of perturbations in myocardial lipid metabolism in the pathogenesis of inherited and acquired forms of heart failure.

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Section: Discussionmentioning

confidence: 98%

A novel mouse model of lipotoxic cardiomyopathy

Chiu

Kovács²,

Ford³

et al. 2001

J. Clin. Invest.

690

562

View full text Add to dashboard Cite

show abstract

“…Furthermore, under these conditions loss of 14 Interestingly, the initial mTAG oxidation rate was higher than subsequent rates [126,155,156], suggesting multiple intracellular TAG pools.…”

mentioning

confidence: 86%

“…ACCEPTED MANUSCRIPT 27 oxidation, but also cardiac dysfunction [132,156,165,166]. TAG turnover is uncoupled from energy demand in heart failure [118,163].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…TAG increases in diabetic hearts on acute fasting accompany diastolic dysfunction [171], though prolonged fasting improves insulin sensitivity, decreases mTAG and improves cardiac function, suggesting a diversion of TAG-derived FA tooxidation [172]. However, rates of mTAG oxidation in diabetic hearts have been reported as similar to controls [156,165], suggesting that associated elevated NEFA concentrations may increase mTAG pool size but have only modest effects on mTAG pool turnover. STZ-diabetic rat hearts have increased mTAG content and turnover when perfused with high NEFA (1.2mM palmitate); at lower NEFA (0.5mM) concentrations, diabetic hearts still have increased TAG turnover, but mTAG content is unchanged [160].…”

mentioning

confidence: 99%

“…Diabetes is characterised by increased cardiac FA metabolism, with increased mTAG content [156,165,170] and impaired LV function [170]. TAG increases in diabetic hearts on acute fasting accompany diastolic dysfunction [171], though prolonged fasting improves insulin sensitivity, decreases mTAG and improves cardiac function, suggesting a diversion of TAG-derived FA tooxidation [172].…”

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confidence: 99%

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The role of triacylglycerol in cardiac energy provision

Evans

Hui‐Kang

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Triacylglycerols (TAG) constitute the main energy storage resource in mammals, by virtue of their high energy density. This in turn is a function of their highly reduced state and hydrophobicity.Limited water solubility, however, imposes specific requirements for delivery and uptake mechanisms on TAG-utilising tissues, including the heart, as well as intracellular disposition. TAGs constitute potentially the major energy supply for working myocardium, both through bloodborne provision and as intracellular TAG within lipid droplets, but also provide the heart with fatty acids (FA) which the myocardium cannot itself synthesise but are required for glycerolipid derivatives with (non-energetic) functions, including membrane phospholipids and lipid signalling molecules. Furthermore they serve to buffer potentially toxic amphipathic fatty acid derivatives.Intracellular handling and disposition of TAGs and their FA and glycerolipid derivatives similarly requires dedicated mechanisms in view of their hydrophobic character. Dysregulation of utilisation can result in inadequate energy provision, accumulation of TAG and/or esterified species, and these may be responsible for significant cardiac dysfunction in a variety of disease states. This review will focus on the role of TAG in myocardial energy provision, by providing FAs from exogenous and endogenous TAG sources for mitochondrial oxidation and ATP production, and how this can change in disease and impact on cardiac function. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 3Key words:heart; triacylglycerol; very-low-density lipoprotein; VLDL; chylomicron; lipid droplet Highlights: Triacylglycerols are supplied to the myocardium within chylomicrons and VLDL  Heart assimilates triacylglycerol-rich lipoproteins by LPL and receptor-mediated routes  Exogenous triacylglycerol-derived fatty acids enter an intracellular lipid pool  Intracardiac triacylglycerol is an important source of fatty acids for oxidation  Dysregulation of triacylglycerol metabolism is associated with cardiac dysfunction

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Biochemical and functional changes in hearts from rabbits with diabetes

1985

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Biochemical and myocardial functional changes were determined in rabbits made diabetic with alloxan (100 mg/kg, intravenously, two injections 24 h apart). Alloxan-induced diabetes was characterized by a state of hypoinsulinaemia and hyperglycaemia. After 10 weeks of diabetes, significant decreases in heart and left ventricular weights as well as increased serum and heart triglycerides and cholesterol were observed in the diabetic animals (p less than 0.05). In addition, left ventricular pressure, heart rate and rate of left ventricular pressure development were all decreased in the animals. The diabetic state was also associated with a slight elevation in myocardial calcium and a significant decrease in magnesium levels (p less than 0.05). Subcellular fractionation of diabetic hearts indicated the presence of alterations in myofibrillar and sarcoplasmic reticulum marker enzymes (p less than 0.05). Among the lysosomal enzymes, measured, N-acetyl-beta-glucosaminidase activity was significantly increased in the homogenates of diabetic left ventricles (p less than 0.05). These alterations in hearts of diabetic rabbits may be responsible for some aspects of diabetic cardiomyopathy.

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Endogenous triacylglycerol metabolism in diabetic heart

Cited by 64 publications

References 0 publications

A novel mouse model of lipotoxic cardiomyopathy

A novel mouse model of lipotoxic cardiomyopathy

The role of triacylglycerol in cardiac energy provision

Biochemical and functional changes in hearts from rabbits with diabetes

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