Myocardial Oxygen Consumption Change Predicts Left Ventricular Relaxation Improvement in Obese Humans After Weight Loss

Lin, Chien‐Jung; Kurup, Suraj; Herrero, Pilar; Schechtman, Kenneth B.; Eagon, J. Christopher; Klein, Samuel; Dávila‐Román, Víctor G.; Stein, Richard I.; Dorn, Gerald W.; Gropler, Robert J.; Peterson, Linda R.

doi:10.1038/oby.2011.186

Cited by 68 publications

(42 citation statements)

References 35 publications

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“…In accordance with this view, a recent study by Lin et al (27) reported reduced oxygen consumption in hearts from obese patients subjected to dietary weight loss. The authors argued that the reduced oxygen consumption could independently predict improved LV relaxation (23), which in turn implies that myocardial oxygen consumption may be mechanistically important in determining cardiac relaxation.…”

Section: Discussionsupporting

confidence: 65%

Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice

Lund

Hafstad

Boardman

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Lund J, Hafstad AD, Boardman NT, Rossvoll L, Rolim NP, Ahmed MS, Florholmen G, Attramadal H, Wisløff U, Larsen TS, Aasum E. Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice. Am J Physiol Heart Circ Physiol 308: H823-H829, 2015. First published January 30, 2015; doi:10.1152/ajpheart.00734.2014.-Although exercise training has been demonstrated to have beneficial cardiovascular effects in diabetes, the effect of exercise training on hearts from obese/diabetic models is unclear. In the present study, mice were fed a high-fat diet, which led to obesity, reduced aerobic capacity, development of mild diastolic dysfunction, and impaired glucose tolerance. Following 8 wk on high-fat diet, mice were assigned to 5 weekly high-intensity interval training (HIT) sessions (10 ϫ 4 min at 85-90% of maximum oxygen uptake) or remained sedentary for the next 10 constitutive weeks. HIT increased maximum oxygen uptake by 13%, reduced body weight by 16%, and improved systemic glucose homeostasis. Exercise training was found to normalize diastolic function, attenuate diet-induced changes in myocardial substrate utilization, and dampen cardiac reactive oxygen species content and fibrosis. These changes were accompanied by normalization of obesity-related impairment of mechanical efficiency due to a decrease in work-independent myocardial oxygen consumption. Finally, we found HIT to reduce infarct size by 47% in ex vivo hearts subjected to ischemia-reperfusion. This study therefore demonstrated for the first time that exercise training mediates cardioprotection following ischemia in diet-induced obese mice and that this was associated with oxygen-sparing effects. These findings highlight the importance of optimal myocardial energetics during ischemic stress. cardiac efficiency; myocardial oxygen consumption; mechanoenergetics; high-intensity exercise; diet-induced obesity THERE HAS BEEN a dramatic transition from physical activity to sedentary lifestyle during the last century. This has resulted in an epidemic increase in the prevalence of metabolic syndrome, obesity, and diabetes, all of which increase the risk of developing cardiovascular and metabolic disorders (15, 42). Cardiovascular diseases are the major causes of morbidity and mortality in type 2 diabetic patients (25) who are at higher risk of developing heart failure, angina, acute myocardial infarction, and dying from an acute myocardial infarction (2).Diabetes-related cardiac complications are due to increased coronary artery disease as well as the development of a specific diabetic cardiomyopathy characterized by ventricular dysfunction in the absence of coronary artery disease or hypertension (24). Although the pathogenesis of diabetes/obesity-related cardiomyopathy is multifactorial and complex, decreased cardiac efficiency seems to play an essential role and is an early hallmark of the diabetic heart (5, 9, 22, 36).Physical training is a well-documented measure to reduce the development of obesity/diabetes, as well as an effec...

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Section: Discussionsupporting

confidence: 65%

Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice

Lund

Hafstad

Boardman

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…In support of UCPs contributing to the metabolic derangements in diabetes, mitochondria isolated from diabetic mouse hearts have elevated rates of oxygen consumption, increased uncoupled respiration, and reduced efficiency (13). Similar phenotypes have been observed in the hearts of diabetic patients through the use of positron emission tomography (PET) metabolic imaging (59).…”

Section: Cardiac Mitochondria In Diabetesmentioning

confidence: 68%

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

Schilling

2015

Antioxidants & Redox Signaling

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Significance: Diabetes is an important risk factor for the development of heart failure (HF). Given the increasing prevalence of diabetes in the population, strategies are needed to reduce the burden of HF in these patients. Recent Advances: Diabetes is associated with several pathologic findings in the heart including dysregulated metabolism, lipid accumulation, oxidative stress, and inflammation. Emerging evidence suggests that mitochondrial dysfunction may be a central mediator of these pathologic responses. The development of therapeutic approaches targeting mitochondrial biology holds promise for the management of HF in diabetic patients. Critical Issues: Despite significant data implicating mitochondrial pathology in diabetic cardiomyopathy, the optimal pharmacologic approach to improve mitochondrial function remains undefined. Future Directions: Detailed mechanistic studies coupled with more robust clinical phenotyping will be necessary to develop novel approaches to improve cardiac function in diabetes. Moreover, understanding the interplay between diabetes and other cardiac stressors (hypertension, ischemia, and valvular disease) will be of the utmost importance for clinical translation of scientific discoveries made in this field. Antioxid. Redox Signal. 22, 1515Signal. 22, -1526

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“…Weight-loss interventions have not only been shown to decrease myocardial FFA uptake without changing insulinstimulated myocardial glucose uptake, 110 but also to reduce myocardial fatty acid oxidation (per gram of LV), and that this decreased fatty acid oxidation is linked to decreased myocardial oxygen consumption (myocardial oxygen uptake per gram of LV). 111 When put together, this strengthens the evidence that increased fatty acid uptake and oxidation in obesity is linked to decreased cardiac efficiency, and that weight loss partially reverses these effects. In addition to this, moderate dietary weight loss has been shown to significantly reduce myocardial triglyceride content 112 and improve both myocardial energetics and diastolic function in obese subjects without cardiovascular risk factors.…”

Section: The Effects Of Weight Loss On Myocardial Metabolismmentioning

confidence: 48%

Myocardial substrate metabolism in obesity

et al. 2012

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Obesity is linked to a wide variety of cardiac changes, from subclinical diastolic dysfunction to end-stage systolic heart failure. Obesity causes changes in cardiac metabolism, which make ATP production and utilization less efficient, producing functional consequences that are linked to the increased rate of heart failure in this population. As a result of the increases in circulating fatty acids and insulin resistance that accompanies excess fat storage, several of the proteins and genes that are responsible for fatty acid uptake and metabolism are upregulated, and the metabolic machinery responsible for glucose utilization and oxidation are inhibited. The resultant increase in fatty acid metabolism, and the inherent alterations in the proteins of the electron transport chain used to create the gradient needed to drive mitochondrial ATP production, results in a decrease in efficiency of cardiac work and a relative increase in oxygen usage. These changes in cardiac mitochondrial metabolism are potential therapeutic targets for the treatment and prevention of obesity-related heart failure. (2013) Keywords: myocardial metabolism; review; obese INTRODUCTION Cardiac energy metabolism is essentially a four-step process involving the following: (1) myocellular substrate uptake/selection, (2) mitochondrial ATP production and (3) ATP transfer from the site of production (mitochondrion) to (4) the site of ATP utilization (cardiac myofibril; Figure 1). 1 Although glycolysis is an ATP generator, the overall ATP production is controlled largely by the rate at which the Krebs (tricarboxylic acid) cycle operates. 2 Acetyl co-enzyme A (CoA), which is produced from the oxidation of fatty acids, ketone bodies, or glucose via glycolysis, and the pyruvate dehydrogenase (PDH) enzyme complex 3 enters the Krebs cycle for complete oxidation. During oxidative phosphorylation, electrons, primarily obtained from oxidative metabolism of carbohydrates and fats, are transferred through the electron transport chain, a fourcomplex protein system embedded within the inner membrane of the mitochondria. The major function of the electron transport chain is to produce a proton electrochemical potential difference between two compartments that powers ATP synthase to generate ATP, which is used for all cardiac cellular processes. 4 ATP is the heart's only immediate source of energy for contraction, and as both systole and diastole are ATP-consuming processes, 5,6 cardiac ATP demand is very high. To keep up with this demand for continuous and efficient contraction and relaxation, the heart needs to produce around 20 times its own weight in ATP per day. 1 As a result of this large energy requirement, any impairment in ATP production, transfer or utilization can have detrimental effects on cardiac function. 7 Cardiac metabolism and ATP production is altered in obesity and has emerged as a candidate mechanism to explain the increase in heart failure in this population. 8 Indeed, it has recently been shown that obesity, in the absence of co-morbiditie...

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Myocardial Oxygen Consumption Change Predicts Left Ventricular Relaxation Improvement in Obese Humans After Weight Loss

Cited by 68 publications

References 35 publications

Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice

Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

Myocardial substrate metabolism in obesity

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