Utilisation of triacylglycerol and non-esterified fatty acid by the working rat heart: myocardial lipid substrate preference

Hui‐Kang, David; Bennett, Mark J.; Evans, Rhys

doi:10.1016/s1388-1981(01)00146-9

Cited by 48 publications

(76 citation statements)

References 51 publications

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“…Whilst synthetic CM-like TAG emulsion is utilised by mouse heart more than liver, skeletal muscle or adipose tissue, only about half this rate was found with mouse VLDL injected into mice in vivo [45], whilst NEFA uptake is comparable to other tissues, implying that myocardial TAG utilisation exceeds that of NEFA [45]. Together, these findings support the notion that plasma TAG are a quantitatively important cardiac substrate, especially in view of the compromised cardiac function in heart-specific cardiac LPL-KO mice with accompanying impaired cardiac VLDL utilisation [44], though acute studies in isolated rat hearts failed to show a significant influence of TGRLPs on cardiac function [16]. The importance of plasma TAG as a muscle fuel was shown in mice overexpressing LPL in muscle alone: this rescues the global LPL-KO mice from neonatal (hyperlipidemic) death [46], normalising plasma VLDL [47].…”

Section: Accepted M Manuscriptsupporting

confidence: 53%

“…This limited VLDL utilisation was not suppressed by NEFA when co-perfused, unlike CM utilisation which was decreased by NEFA [16], suggesting distinct pathways of utilisation. Of the VLDL-TAG-FA assimilated, about one quarter was incorporated into tissue lipids whilst the remainder was oxidised; by contrast, about 90% of CM-TAG was oxidised; the metabolic partitioning was not affected by NEFA [16]. Comparable results have also been reported [15,22,23].…”

Section: Cardiac Vldl-tag Utilisationmentioning

confidence: 77%

“…FA/min/g)) and CM (~ 75nmol FA/min/g) when each was compared as sole lipid substrate (0.4mM) [16]. This limited VLDL utilisation was not suppressed by NEFA when co-perfused, unlike CM utilisation which was decreased by NEFA [16], suggesting distinct pathways of utilisation.…”

Section: Cardiac Vldl-tag Utilisationmentioning

confidence: 87%

“…Rat hearts perfused with rat CM utilised CM-TAG to about the same extent as NEFA when each were compared as sole lipid substrates [15,16] and CM could maintain cardiac mechanical function; most (83%) of the CM-TAG assimilated was oxidised, the remainder was esterified mostly into cellular TAG [15,16]. NEFA did inhibit CM-TAG utilisation when co-perfused, and this was entirely due to decreased CM-TAG oxidation, but CM did not suppress myocardial NEFA uptake and metabolism [16]. Together, these observations imply that NEFA-derived FA are more likely to be oxidised and CM-TAG-derived FAs more likely to be esterified [14] suggesting that there may be discrete partitioning between non-esterified and CM-TAG-derived FA.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…It is likely that there is constitutive enzyme expression, perhaps reflecting the availability of VLDL-TAG regardless of nutritional status. Plasma TAG may modulate LPL and hence cardiac TAG assimilation [58,68], and TGRLPs modified heparin-releasable H-LPL activity [16]. Other…”

Section: Lipoprotein Lipase Mediated Myocardial Tag Uptakementioning

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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Section: Accepted M Manuscriptsupporting

confidence: 53%

Section: Cardiac Vldl-tag Utilisationmentioning

confidence: 77%

Section: Cardiac Vldl-tag Utilisationmentioning

confidence: 87%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Lipoprotein Lipase Mediated Myocardial Tag Uptakementioning

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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Novel Strategies to Prevent Total Parenteral Nutrition‐Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes

Lucchinetti

Lou

Wawrzyniak

et al. 2020

Molecular Nutrition Food Res

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Total parenteral nutrition (TPN) is a life‐saving therapy administered to millions of patients. However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN‐associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described. The role of the bile acid receptors farnesoid X receptor and Takeda G protein‐coupled receptor, of pleiotropic hormones, and growth factors is highlighted, and the mechanisms of insulin resistance, namely the lack of insulinotropic and insulinomimetic signaling of gut‐originating incretins as well as the potentially toxicity of phytosterols and pro‐inflammatory fatty acids mainly released from soybean oil‐based lipid emulsions, are discussed. Finally, novel approaches in the design of next generation lipid delivery systems are proposed. Propositions include modifying the physicochemical properties of lipid emulsions, the use of lipid emulsions generated from sustainable oils with favorable ratios of anti‐inflammatory n‐3 to pro‐inflammatory n‐6 fatty acids, beneficial adjuncts to TPN, and concomitant pharmacotherapies to mitigate TPN‐associated adverse effects.

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Regulation of Fatty Acid Oxidation of the Heart

Folmes¹,

Lopaschuk²

2007

Mitochondria

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Utilisation of triacylglycerol and non-esterified fatty acid by the working rat heart: myocardial lipid substrate preference

Cited by 48 publications

References 51 publications

The role of triacylglycerol in cardiac energy provision

The role of triacylglycerol in cardiac energy provision

Novel Strategies to Prevent Total Parenteral Nutrition‐Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes

Regulation of Fatty Acid Oxidation of the Heart

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