Association of plasma free fatty acids and left ventricular diastolic function in patients with clinically severe obesity

Leichman, Joshua G.; Aguilar, David; King, Terri M.; Vlada, Adrian C.; Reyes, Manuel; Taegtmeyer, Heinrich

doi:10.1093/ajcn/84.2.336

Cited by 65 publications

(32 citation statements)

References 42 publications

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“…94 However it is not known whether this relationship is causal or whether elevated fatty acids directly and adversely effect cardiac function in diabetic patients. Elevated plasma fatty acid levels are also modestly correlated with a decreased diastolic function (rϭ0.33) in severely obese patients, 95 but, again, a causal role of fatty acids or cardiac lipid accumulation in diastolic dysfunction has not been demonstrated. Experimental studies in the perfused rat and mouse hearts have also shown that accelerated fatty acid oxidation contributes to the development of diabetic cardiomyopathies by inhibiting glucose oxidation and lowering cardiac mechanical efficiency 77,96 -98 and that pharmacologically inhibiting fatty acid metabolism and increasing glucose metabolism improves contractile function in diabetes.…”

Section: Circulating Fatty Acids and Cardiac Pathology In Obesitymentioning

confidence: 99%

Cardiac Energy Metabolism in Obesity

Lopaschuk

Folmes²,

Stanley

2007

Circulation Research

253

208

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Abstract-Obesity results in marked alterations in cardiac energy metabolism, with a prominent effect being an increase in fatty acid uptake and oxidation by the heart. Obesity also results in dramatic changes in the release of adipokines, such as leptin and adiponectin, both of which have emerged as important regulators of cardiac energy metabolism. The link among obesity, cardiovascular disease, lipid metabolism, and adipokine signaling is complex and not well understood. However, optimizing cardiac energy metabolism in obese subjects may be one approach to preventing and treating cardiac dysfunction that can develop in this population. This review discusses what is presently known about the effects of obesity and the impact adipokines have on cardiac energy metabolism and insulin signaling. The clinical implications of obesity and energy metabolism on cardiac disease are also discussed. (Circ Res. 2007;101:335-347.)

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Section: Circulating Fatty Acids and Cardiac Pathology In Obesitymentioning

confidence: 99%

Cardiac Energy Metabolism in Obesity

Lopaschuk

Folmes²,

Stanley

2007

Circulation Research

253

208

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“…7 In severely obese patients with a body mass index Ͼ50, the serum concentrations of nonesterified fatty acid show a negative association with load-independent diastolic function. 8 In addition to hemodynamic changes, obesity is also associated with increased risk of atrial fibrillation 9 and ventricular ectopic activity. 10 The mechanisms of cardiac remodeling with obesity are complex.…”

Section: Heart Muscle Disease In Human Obesitymentioning

confidence: 99%

Adaptation and Maladaptation of the Heart in Obesity

Harmancey¹,

Wilson²,

Taegtmeyer³

2008

Hypertension

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O besity appears to be a major cause of hypertension and associated cardiovascular pathophysiology, including cardiac dysfunction. However, obesity may lead to abnormal cardiac function through mechanisms that are independent of, or that act in concert with, hypertension. One hypothesis of obesity-induced cardiac dysfunction is that an oversupply of substrates leads first to adaptive changes and eventually to contractile dysfunction of the heart. We reason that increased supply of nonesterified fatty acids, together with metabolic dysregulation in obesity, including an inadequate activation of fat oxidation, results in the accumulation of toxic lipid byproducts and subsequent contractile dysfunction. Although the phenomenon may have already been known to Virchow 1 when he described "fatty metamorphosis" of the heart, the concept of cardiac "lipotoxicity" re-emerged only recently with its description in the heart of the obese Zucker diabetic fatty rat. 2 The concept is, however, still a hypothesis rather than an established physiological principle. In spite of the many investigations performed in rodent models, the mechanism(s) responsible for impaired contractile function of the heart is still obscure, and it is uncertain whether lipid metabolites contribute to "obesity cardiomyopathy" in humans. Our brief review is an attempt to understand the chronic regulatory effects of changes in systemic metabolism on cardiac function. In other words, we discuss current concepts of cardiac adaptation and maladaptation to a deranged metabolic environment. Heart Muscle Disease in Human ObesityChanges in cardiovascular function in the setting of clinically severe obesity were first reported in obese volunteers undergoing cardiac catheterization. The patients demonstrated reduced left ventricular (LV) compliance and a decrease in stroke work index in the presence of increased LV end diastolic pressure that correlated with the severity of obesity. 3 There is a significant correlation between obesity and LV mass, even after controlling for age and blood pressure, 4 and there is also a significant correlation between weight and impaired diastolic filling of the left ventricle. 5 Both systolic and diastolic function are decreased in otherwise healthy obese young women. 6 In the same population there is a decrease of cardiac efficiency. 7 In severely obese patients with a body mass index Ͼ50, the serum concentrations of nonesterified fatty acid show a negative association with load-independent diastolic function. 8 In addition to hemodynamic changes, obesity is also associated with increased risk of atrial fibrillation 9 and ventricular ectopic activity. 10 The mechanisms of cardiac remodeling with obesity are complex. 11,12 A major obstacle in any attempt to characterize "obesity cardiomyopathy" is the prevalence of comorbid disorders and confounding variables, such as the metabolic syndrome, 13 insulin resistance, hypertension, type 2 diabetes, and physical inactivity. It is of note that both increased blood pressure and increase...

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“…In addition, LV biopsies from human hearts undergoing LV assist device implantation for heart failure demonstrate that patients with obesity or diabetes and heart failure have more accumulation of lipid within the myocardium than those with heart failure from other causes [60]. Also more indirectly supporting the theory that excessive FAs may contribute to LV dysfunction in obesity are results from a study relating plasma free FAs an LV diastolic dysfunction [61]. Further studies, including longitudinal and interventional studies are still needed in humans to prove that lipotoxicity occurs as it does in animal models.…”

Section: Obesity and Myocardial Metabolismmentioning

confidence: 92%

Cardiovascular consequences of obesity and targets for treatment

Mittendorfer

Peterson

2008

Drug Discovery Today: Therapeutic Strategies

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Obesity is a risk factor for cardiovascular disease, including coronary artery disease and heart failure, but the mechanisms by which it may cause them are not completely clear. Currently, therapies aimed at obesity-related cardiovascular disease include weight loss strategies and reduction of the other risk factors that are associated with obesity and cardiovascular disease. Other pathways with for potential drug development for obesity-related CVD are also discussed. Keywordsobesity; myocardium; metabolism; systolic function; diastolic function; coronary artery disease Cardiovascular disease (CVD) is still the leading cause of death in developed countries, despite a recent decline in coronary artery disease-related deaths. In the United States approximately 35% of all deaths are due to CVD [1]. Obesity (defined as a body mass index [BMI] of ≥ 30 kg/m 2 ) is a risk factor for CVD, especially coronary heart disease and heart failure. It is estimated that the relative risk of coronary heart disease in obesity is approximately 1.5 even after adjusting for all other traditional coronary heart disease risk factors that often co-migrate with obesity (e.g. hyperlipidemia, hypertension) [2]. Obesity also is associated with an increased risk of heart failure, with ~11 -14% of all heart failure thought to be attributable to obesity [3]. Given that excess body weight now affects more than 300 million persons worldwide, prevention and treatment of obesity should be considered one of the cornerstones for the prevention of CVD (http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/). This review will focus on the impact of obesity on CVD, particularly atherosclerotic coronary artery disease and heart failure and treatment of obesity-related heart disease.

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Association of plasma free fatty acids and left ventricular diastolic function in patients with clinically severe obesity

Cited by 65 publications

References 42 publications

Cardiac Energy Metabolism in Obesity

Cardiac Energy Metabolism in Obesity

Adaptation and Maladaptation of the Heart in Obesity

Cardiovascular consequences of obesity and targets for treatment

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