Fatty acid homeostasis in the normoxic and ischemic heart

Vusse, Ger J.; Glatz, Jan F. C.; Stam, H.; Reneman, Robert S.

doi:10.1152/physrev.1992.72.4.881

Cited by 470 publications

(323 citation statements)

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“…The FFA in the blood, before binding to albumin, are mainly released from the body's adipose tissue. 44 Arterial FFA concentration and in¯ow (¯ow Â concentration) have been shown to be strongly coupled to leg FFA uptake at rest and during exercise. 45,46 Lipoprotein lipase, which is attached to the luminal surface of the endothelial cells, hydrolyses the triacylglycerol core of chylomicrons and VLDL.…”

Section: Fatty Acid Delivery and Transportmentioning

confidence: 99%

“…32 ± 34,39 ± 41 Wolfe et al 42 and Webber et al 43 also reported a decreased rate of appearance of FFA per kg fat mass during fasting in obese compared to lean males. However, when expressed per kg of lean body mass, FFA turnover is higher in obese or upper-body obese than in lean or lower body obese subjects 43,44 (Figure 1). Also the response of the glycerol and FFA rates of appearance per kg fat mass to adrenaline infusion is signi®cantly blunted in the obese.…”

Section: Introductionmentioning

confidence: 97%

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Exercise training and substrate utilisation in obesity

Baak

1999

Int J Obes

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Together with diet and behavioural modi®cation, regular exercise is one of the key components of programs for the treatment of obesity. It appears to be one of the major factors determining the long-term success of weight loss programs. One of the mechanisms that may underlie this and other bene®cial effects of regular exercise is the effect of exercise training on substrate utilisation. Exercise training increases fat oxidation in lean subjects. The capacity to mobilise and oxidise fat has been shown to be impaired in obese and post-obese subjects. Thus, an increase in the capacity for fat oxidation may help to maintain fat and energy balance at a lower fat mass in individuals with a predisposition for obesity. However, in view of the impaired fat oxidation in obese and post-obese individuals the question arises whether exercise training also increases fat oxidation in the obese. Few studies have addressed this question and have investigated the effect of exercise training on substrate utilisation in obesity. Addition of an exercise training program has been shown to prevent the reduction of basal fat oxidation that is associated with dietinduced weight loss in two studies. No effect of additional exercise training on substrate oxidation during exercise was found. In post-obese subjects exercise training caused no change in 24 h substrate oxidation in one study and increased carbohydrate, rather than fat oxidation in another. In obese subjects neither low (40% maximal aerobic ®tness (VO 2 max)) nor high (70% VO 2 max) intensity training was found to affect resting substrate oxidation. During exercise fractional fat oxidation was increased after low, but not after high intensity training. The question, whether exercise training increases fat oxidation in obese and post-obese as in lean subjects therefore cannot be answered conclusively at this point in time and requires further study. The role of exercise intensity and type of exercise needs to be studied as well.

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Section: Fatty Acid Delivery and Transportmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Exercise training and substrate utilisation in obesity

Baak

1999

Int J Obes

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“…Mitochondrial oxidation of long‐chain fatty acids (FAs) accounts for 60% to 90% of the energy used by the adult heart under normal physiological conditions, with glucose and lactate oxidation providing the remainder 1, 2, 3, 4. The healthy heart is metabolically flexible and can readily switch between energy substrates as dictated by substrate availability, hormonal status, and physiological environment 5.…”

Section: Introductionmentioning

confidence: 99%

Modeling the Transition From Decompensated to Pathological Hypertrophy

Pascual

Schisler

Grevengoed

et al. 2018

JAHA

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BackgroundLong‐chain acyl‐CoA synthetases (ACSL) catalyze the conversion of long‐chain fatty acids to fatty acyl‐CoAs. Cardiac‐specific ACSL1 temporal knockout at 2 months results in a shift from FA oxidation toward glycolysis that promotes mTORC1‐mediated ventricular hypertrophy. We used unbiased metabolomics and gene expression analyses to examine the early effects of genetic inactivation of fatty acid oxidation on cardiac metabolism, hypertrophy development, and function.Methods and ResultsGlobal cardiac transcriptional analysis revealed differential expression of genes involved in cardiac metabolism, fibrosis, and hypertrophy development in Acsl1 H−/− hearts 2 weeks after Acsl1 ablation. Comparison of the 2‐ and 10‐week transcriptional responses uncovered 137 genes whose expression was uniquely changed upon knockdown of cardiac ACSL1, including the distinct upregulation of fibrosis genes, a phenomenon not observed after complete ACSL1 knockout. Metabolomic analysis identified metabolites altered in hearts displaying partially reduced ACSL activity, and rapamycin treatment normalized the cardiac metabolomic fingerprint.ConclusionsShort‐term cardiac‐specific ACSL1 inactivation resulted in metabolic and transcriptional derangements distinct from those observed upon complete ACSL1 knockout, suggesting heart‐specific mTOR (mechanistic target of rapamycin) signaling that occurs during the early stages of substrate switching. The hypertrophy observed with partial Acsl1 ablation occurs in the context of normal cardiac function and is reminiscent of a physiological process, making this a useful model to study the transition from physiological to pathological hypertrophy.

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“…Although kinetics of this tracer were originally studied using a six-compartment model, the limited time resolution of a PET study forced a reduction to a simplified two-tissue compartment model describing uptake (and back diffusion) and (irreversible)Finally, [ 11 C]palmitate can be used to study uptake and utilization of long-chain fatty acids, which play a dominant role in delivering energy to the heart. Since fatty acid metabolism [8] is affected by a number of pathophysiological conditions, [ 11 C]palmitate has been used to study myocardial metabolism in various diseases such as viral infections and diabetes [5,10]. Most studies involving [ 11 C]palmitate used semiquantitative analyses to describe its kinetics.…”

Section: Introductionmentioning

confidence: 99%

Kinetic models for analysing myocardial [11C]palmitate data

Jong

Rijzewijk

Lubberink

et al. 2009

Eur J Nucl Med Mol Imaging

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Purpose [ 11 C]Palmitate PET can be used to study myocardial fatty acid metabolism in vivo. Several models have been applied to describe and quantify its kinetics, but to date no systematic analysis has been performed to define the most suitable model. Methods In this study a total of 21 plasma input models comprising one to three compartments and up to six free rate constants were compared using statistical analysis of clinical data and simulations. To this end, 14 healthy volunteers were scanned using [ 11 C]palmitate, whilst myocardial blood flow was measured using H 2 15 O. Results Models including an oxidative pathway, representing production of 11 CO 2 , provided significantly better fits to the data than other models. Model robustness was increased by fixing efflux of 11 CO 2 to the oxidation rate. Simulations showed that a three-tissue compartment model describing oxidation and esterification was feasible when no more than three free rate constants were included. Conclusion Although further studies in patients are required to substantiate this choice, based on the accuracy of data description, the number of free parameters and generality, the three-tissue model with three free rate constants was the model of choice for describing [ 11 C] palmitate kinetics in terms of oxidation and fatty acid accumulation in the cell.

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Fatty acid homeostasis in the normoxic and ischemic heart

Cited by 470 publications

References 0 publications

Exercise training and substrate utilisation in obesity

Exercise training and substrate utilisation in obesity

Modeling the Transition From Decompensated to Pathological Hypertrophy

Kinetic models for analysing myocardial [11C]palmitate data

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