Myocardial Lipid and Carbohydrate Metabolism in Healthy, Fasting Men at Rest: Studies During Continuous Infusion of <sup>3</sup>H‐Palmitate

Lassers, B. W.; Kaijser, L.; Carlson, Lars A.

doi:10.1111/j.1365-2362.1972.tb00661.x

Cited by 78 publications

(42 citation statements)

References 31 publications

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“…in our study, similar to the findings of Lassers et al (11). It should be acknowledged that secretion of triglyceridecontaining lipoproteins by the heart, which has been reported in rodents (14), would result in an underestimate of myocardial uptake of circulating triglycerides.…”

Section: Ffa and Triglyceride Uptake By The Heartsupporting

confidence: 92%

“…Previous reports (10,11) suggested triglyceride hydrolysis by the heart, presumably by myocardial LPL (LPL c ), but did not determine whether the fatty acids generated were taken up by the myocardium or whether they spilled over into the systemic circulation. The extraction of unlabeled triglyceride in the present study was significant in 3 of 6 subjects, but not for the group (P ϭ 0.12), consistent with a previous report in which significant uptake of unlabeled triglyceride was observed in 9 of 17 subjects (11); this is likely a reflection of the difficulty in detecting very small arteriovenous concentration differences.…”

Section: Discussionmentioning

confidence: 99%

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Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

et al. 2007

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Animal studies indicate that oversupply of fatty acids derived from the action of cardiac lipoprotein lipase (LPL) on plasma lipoproteins may contribute to myocardial dysfunction. However, the contribution of circulating triglycerides to myocardial fatty acid supply in humans is not known. Six postabsorptive nondiabetic subjects who were scheduled for diagnostic coronary angiography were studied. 14 C oleate and a lipid emulsion labeled with 3 H triolein were infused to assess myocardial uptake of free fatty acids (FFAs) and triglycerides, as well as myocardial spillover of LPL-generated fatty acids. Six paired blood samples were taken from the femoral artery and the coronary sinus. Coronary sinus concentrations of unlabeled triglycerides were slightly, but not significantly, lower than arterial (P ‫؍‬ 0.12), whereas labeled triglyceride concentrations were significantly lower in the coronary sinus than in the artery (P < 0.05; extraction fraction Х11%). Triglycerides and FFAs accounted for ϳ17% and ϳ83%, respectively, of myocardial fatty acid uptake. Systemic and myocardial fractional spillover of LPL-generated fatty acids was 49.0 ؎ 7% and 34.7 ؎ 13%, respectively. The myocardium was a minor contributor to systemic triglyceride uptake (ϳ3%) and a trivial contributor to systemic FFA production (ϳ0.5%). These results indicate that circulating triglycerides may be a significant source of fatty acids for myocardial respiration. Diabetes 56:527-530, 2007 I t has been suggested that free fatty acids (FFAs) are the primary energy source for the myocardium (1). However, the heart contains a considerable amount of lipoprotein lipase (LPL) (2), and studies in animals have found significant triglyceride uptake by the myocardium. It has been suggested recently that circulating triglycerides are actually the primary lipid fuel for this tissue (3). Very little information on the role of triglycerides in human myocardial metabolism is available, however. The present study was therefore undertaken to determine whether significant uptake of triglycerides occurs in the heart and also to determine the relative role of triglycerides and FFAs in the provision of lipid fuel to that tissue. RESEARCH DESIGN AND METHODSInformed written consent was obtained from six Caucasian subjects (three male, three female; average age 65 years, weight 91.3 kg, BMI 30.9 kg/m 2 ) scheduled for diagnostic coronary angiography. Individuals with diabetes, significant hypertriglyceridemia (Ͼ2.26 mmol/l), congestive heart failure, unstable angina, recent stroke, previous myocardial infarction or angioplasty, left ventricular ejection fraction Ͻ45%, or significant endocrine, hepatic, or renal disorders were excluded. Five of the six subjects proved to have coronary artery disease; four of these underwent percutaneous stent placement. One subject had valve replacement surgery for aortic stenosis.Subjects were studied according to a protocol approved by the Mayo Institutional Review Board. On the morning of the study (after an overnight fast and after ob...

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Section: Ffa and Triglyceride Uptake By The Heartsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

et al. 2007

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“…The latter data are similar to those reported in catheterization studies [21] and support, together with several additional in vivo observations (vide infra) the view that glucose uptake measured with FDG and PET provides information which is fully compatible with physiological knowledge. Similarly, concentrations of plasma NEFA are inversely correlated with rates of FDG uptake [12] and arterial-coronary sinus glucose differences [22]. Several indices of cardiac work are also directly correlated with glucose uptake under normoglycaemic hyperinsulinaemic conditions [12,14,23] where glucose is the main fuel for heart energy production.…”

Section: Discussionmentioning

confidence: 86%

Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM

et al. 1998

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Signs or symptoms of macrovascular disease are frequently found even prior to the development of noninsulin-dependent diabetes mellitus (NIDDM) [1]. This suggests that coronary heart disease (CHD) and NIDDM share a pathophysiologic feature, which predisposes to both diseases. Classic risk factors such as serum cholesterol, age, gender, hypertension and smoking explain only a fraction of the 2±4-fold increase in cardiovascular mortality in patients with NIDDM [1,2]. Insulin resistance, usually measured by quantitating the rate of insulin-stimulated glucose uptake, qualifies as the underlying pathophysiologic abnormality for both CHD and NIDDM, since it predicts, independent of other risk factors, both disorders [3,4].The mechanisms linking insulin resistance to CHD are unclear but could involve lipid abnormalities such as an increase in the concentration of atherogenic small dense LDL particles, which accompanies insu- Diabetologia (1998) Summary Skeletal muscle insulin resistance and coronary heart disease (CHD) often precede non-insulin-dependent diabetes mellitus (NIDDM). A recent study showed the myocardium of patients with CHD to be insulin resistant, independent of blood flow. We determined whether myocardial insulin resistance is a feature of NIDDM patients with no CHD. Skeletal muscle and myocardial glucose uptake were determined in 10 patients with NIDDM and 9 ageand weight-matched normal men of similar age and body mass index men using [18 F]-2-fluoro-2-deoxy-dglucose and positron emission tomography under normoglycaemic hyperinsulinaemic conditions. Whole body glucose uptake, as determined by the euglycaemic clamp technique, was significantly lower in the patients with NIDDM (35 ± 3 mmol/kg body weight´min) than the normal subjects (45 ± 3 mmol/ kg body weight´min, p < 0.02). Insulin-stimulated femoral muscle glucose uptake was significantly lower in the patients with NIDDM (71 ± 6 mmol/kg muscle´min) than in the normal subjects (96 ± 5 mmol/ kg muscle´min, p < 0.01). Whole body glucose uptake was correlated with femoral muscle glucose uptake in the entire group (r = 0.76, p < 0.001), in patients with NIDDM and in normal subjects. Rates of insulin-stimulated myocardial glucose uptake were comparable between the patients with NIDDM (814 ± 76 mmol/kg muscle´min) and the normal subjects (731 ± 63 mmol/kg muscle´min, p > 0.4). Whole body or femoral muscle, and myocardial glucose uptake were not correlated in all subjects, patients with NIDDM or normal subjects. We conclude that insulin resistance of the myocardium is not a feature of uncomplicated NIDDM. [Diabetologia (1998) 41: 555-559] Keywords Myocardium, insulin resistance, non-insulin-dependent diabetes mellitus, positron emission tomography.

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“…In this study the myocardium was only a minor contributor to total systemic TAG (VLDL) uptake (~3%) and systemic NEFA production (~0.5%) [2]. Previous studies had also suggested only limited VLDL-TAG utilisation by the human heart with about 10-20% of cardiac energy deriving from VLDL [31]), suggesting that in human heart, at least in the postabsorptive state, NEFAs may be more important cardiac substrates than VLDL-TAG [30,32]. Since human hearts can assimilate and oxidise large amounts of glucose when deprived of NEFA (and rodent hearts can function normally despite being LPL deficient [33]) these observations suggest that plasma VLDL-TAG is not an essential cardiac fuel.…”

Section: Cardiac Vldl-tag Utilisationmentioning

confidence: 88%

“…In the well-fed state it certainly represents the major transport form of endogenous TAG-FA, synthesised by de novo hepatic lipogenesis and exported to adipose tissue for storage; however, in the post-absorptive state it is assembled in the liver from adipose-derived NEFA, and it is unclear why NEFA cannot supply FA direct to oxidative tissues such as heart. Indeed, this pathway certainly occurs, but the issue of the A C C E P T E D M A N U S C R I P T Studies of cardiac A-V (coronary sinus) differences in non-diabetic patients undergoing cardiac catheterisation (usually in the post-absorptive state) found that some hearts extracted plasma (VLDL)TAG but not others (as previously noted [30]) whilst infused labelled TAG was consistently extracted (extraction fraction ~11%) [2]. TAGs and NEFAs accounted for ~17% and ~83%…”

Section: Cardiac Vldl-tag Utilisationmentioning

confidence: 95%

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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Myocardial Lipid and Carbohydrate Metabolism in Healthy, Fasting Men at Rest: Studies During Continuous Infusion of ³H‐Palmitate

Cited by 78 publications

References 31 publications

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM

The role of triacylglycerol in cardiac energy provision

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Myocardial Lipid and Carbohydrate Metabolism in Healthy, Fasting Men at Rest: Studies During Continuous Infusion of 3H‐Palmitate

Cited by 78 publications

References 31 publications

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

Myocardial Uptake of Circulating Triglycerides in Nondiabetic Patients With Heart Disease

Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM

The role of triacylglycerol in cardiac energy provision

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Resources

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Myocardial Lipid and Carbohydrate Metabolism in Healthy, Fasting Men at Rest: Studies During Continuous Infusion of ³H‐Palmitate