Influence of free fatty acids on myocardial oxygen consumption and ischemic injury

Vik‐Mo, Harald; Mjøs, Ole D.

doi:10.1016/0002-9149(81)90621-4

Cited by 154 publications

(62 citation statements)

References 51 publications

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“…Increased fatty acid uptake and oxidation by the heart can also increase MV O 2 , because more oxygen is required to generate ATP from fatty acid than by glucose metabolism, and increased oxygen may be consumed by fatty acid esterification and reactive oxygen species production. 8,10,27 Our finding that increasing BMI was an independent predictor of decreased efficiency extends the findings of previous ex vivo studies to obese humans. These previous studies demonstrated that increased MV O 2 , MFAUp, and MFAO were associated with decreased efficiency.…”

Section: Discussionsupporting

confidence: 86%

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Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

et al. 2004

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Background-Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance.In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. (rϭ0.58, PϽ0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MV O 2 and efficiency (Pϭ0.0005 and PϽ0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (PϽ0.05, Ͻ0.005, and Ͻ0.005, respectively). Conclusions-In young women, obesity is a significant predictor of increased MV O 2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

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Section: Discussionsupporting

confidence: 86%

“…These previous studies demonstrated that increased MV O 2 , MFAUp, and MFAO were associated with decreased efficiency. [27][28][29] The results of the present study show that obese humans, who have alterations in MV O 2 and myocardial fatty acid metabolism, also have changes in the translation of energy to contractile function.…”

Section: Discussionsupporting

confidence: 52%

Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

et al. 2004

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“…It supports the beneficial effects of oxfenicine on cardiac contractility and enzyme release in the ischemic heart (8,18,21,33,51) and extends the observation to cell death. Other CPT-1 inhibitors such as etoxomir (25) and 2,5,4 chlorophenylpentyloxirane-2-carboxylate (56) confirm the beneficial role of inhibiting CPT-1 on cardiac contractile performance in the ischemic myocardium.…”

Section: Discussionsupporting

confidence: 80%

“…Our data are at variance with that of Paumen et al (37), who found in murine hematopoietic cell lines that etomoxir accentuated palmitate-induced apoptosis. The most likely explanation for the difference is the fact that the different cell types as the beneficial effect of CPT-1 inhibition has been established in the heart (8,18,21,33,51) and confirmed in proximal renal tubular cells subjected to hypoxia (38). Etomoxir differs from oxfenicine, however, in that etomoxir requires metabolism to its CoA ester to become active (46), whereas oxfenicine is transaminated in the heart by branched-chain amino acid aminotransferase to 4-hydroxyphenylglyoxyalte, which acts to directly inhibit CPT-1 (47).…”

Section: Discussionmentioning

confidence: 99%

Palmitate-induced cardiac apoptosis is mediated through CPT-1 but not influenced by glucose and insulin

Kong

Rabkin

2002

American Journal of Physiology-Heart and Circulatory Physiology

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Kong, Jennifer Y., and Simon W. Rabkin. Palmitateinduced cardiac apoptosis is mediated through CPT-1 but not influenced by glucose and insulin. Am J Physiol Heart Circ Physiol 282: H717-H725, 2002; 10.1152/ajpheart.00257. 2001.-To test the hypothesis that regulation of palmitate metabolism, through carnitine palmitoyl transferase-1 (CPT-1) or through alterations of glycolysis, was involved in the pathway of palmitate-mediated cell death, cardiomyocytes were cultured from 7-day-old chick embryos. Palmitateinduced cell death, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, was enhanced by carnitine, a cofactor needed for palmitate transport into mitochondria via CPT-1. Carnitine co-incubation with palmitate significantly (P Ͻ 0.01) increased the amount of apoptotic cells, assessed by propidium iodine staining and fluorescent-activated cell sorting analysis compared with treatment with either palmitate or carnitine alone. The CPT-1 inhibitor oxfenicine significantly (P Ͻ 0.05) blocked the cell death induced by the combination of palmitate and carnitine. The short-chain saturated fatty acid capric acid (100 M), which is not likely transported by CPT-1, did not significantly affect cell viability, whereas the C18 saturated fatty acid stearic (100 M) significantly (P Ͻ 0.01) reduced cell viability and to a similar extent as palmitate. In contrast, there was no significant alteration of palmitate-induced cell death by cotreatment with 100 nM insulin ϩ 2 g/l glucose or 1 mM lactate, which promote ATP generation by glycolysis rather than fatty acid oxidation. Fumonisin did not alter palmitate-induced cell death or apoptosis, suggesting that the effect of palmitate was not operative through increased ceramide synthesis. These results suggest that oxidation of palmitate through CPT-1 is involved in the production of apoptosis in cardiomyocytes.carnitine; fatty acid metabolism; oxfenicine; fumonisin; palmitate; capric acid FATTY ACIDS ARE A PRINCIPAL source of energy for the heart, and the metabolism of fatty acids is of fundamental importance for cardiac function (for reviews, see Refs. 23,24,48). Briefly, fatty acid metabolism involves fatty acids binding to carrier binding proteins that are transported across the sarcolemmal membrane, and once inside the cell are metabolized to long chain acyl-CoA by acyl-CoA synthetase (23,24,48). The acyl moieties are transferred to the mitochondria by a series of enzymes involving carnitine palmitoyl transferase-1 and -2 (CPT-1 and -2) as well as carnitine-acylcarnitine translocase. In the mitochondria, long-chain acyl-CoA is subjected to ␤-oxidation-producing acetyl CoA, a fatty acyl moiety less two carbons, and the by-products, reduced flavin adenine dinucleotide and reduced nicotinamide adenine dinucleotide. Fatty acid oxidation also occurs in peroxisomes (23,24,48) but the amount is small (9).

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“…The ischemic myocardium is exposed to hypoxia due to excessive oxygen consumption during FFA metabolism, which reduces the myocardial uptake of glucose that is required for anaerobic glycolysis and mitochondrial ATP production 40, 41, 42. The excessive uptake of FFAs into myocardium contributes to cardiac function impairment in the ischemic process, which can subsequently increase infarct size and mortality 38, 43…”

Section: Discussionmentioning

confidence: 99%

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

Nishikido

Oyama

Shiraki

et al. 2016

JAHA

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BackgroundAn excessive inflammatory response after myocardial infarction (MI) increases myocardial injury. The toll‐like receptor (TLR)‐4 is activated by the recognition of endogenous ligands and is proinflammatory when there is myocardial tissue injury. The apoptosis inhibitor of the macrophage (AIM) is known to provoke an efflux of saturated free fatty acids (FFA) due to lipolysis, which causes inflammation via the TLR‐4 pathway. Therefore, this study investigated the hypothesis that AIM causes a proinflammatory response after MI.Methods and ResultsThe left anterior descending coronary artery was ligated to induce MI in both AIM‐knockout (AIM−/−) and wild‐type (WT) mice. After 3 days, the inflammatory response from activation of the TLR‐4/NFκB pathway was assessed, and infarct size was measured by staining with triphenyltetrazolium chloride. In addition, left ventricular remodeling was examined after 28 days. Although the area at risk was similar between AIM−/− and WT mice, the infarct size was significantly smaller in AIM−/− mice (P=0.02). The heart weight–to–body weight ratio and myocardial fibrosis were also decreased in the AIM−/− mice, and the 28‐day survival rate was improved (P<0.01). With the reduction of plasma FFA in AIM−/− mice, myocardial IRAK4 and NFκB activity were decreased (all P<0.05). Moreover, there was a reduction in myeloperoxidase activity and inducible nitric oxide synthase as part of the inflammatory response (P<0.01, P=0.03, respectively). Furthermore, NFκB DNA‐binding activation via TLR‐4, neutrophil infiltration, and inflammatory mediators were decreased in AIM−/− mice.ConclusionsThe deletion of AIM reduced the inflammatory response and infarct size and improved survival after myocardial infarction.

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Influence of free fatty acids on myocardial oxygen consumption and ischemic injury

Cited by 154 publications

References 51 publications

Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

Palmitate-induced cardiac apoptosis is mediated through CPT-1 but not influenced by glucose and insulin

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction

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