Adiposity of the heart, revisited.

University of Texas Southwestern Medical Center, Dallas, Texas 75390-8899, USA.
Annals of internal medicine (Impact Factor: 16.1). 05/2006; 144(7):517-24.
Source: PubMed

ABSTRACT Obesity is a major risk factor for heart disease. In the face of obesity's growing prevalence, it is important for physicians to be aware of emerging research of novel mechanisms through which adiposity adversely affects the heart. Conventional wisdom suggests that either hemodynamic (that is, increased cardiac output and hypertension) or metabolic (that is, dyslipidemic) derangements associated with obesity may predispose individuals to coronary artery disease and heart failure. The purpose of this review is to highlight a novel mechanism for heart disease in obesity whereby excessive lipid accumulation within the myocardium is directly cardiotoxic and causes left ventricular remodeling and dilated cardiomyopathy. Studies in animal models of obesity reveal that intracellular accumulation of triglyceride renders organs dysfunctional, which leads to several well-recognized clinical syndromes related to obesity (including type 2 diabetes). In these rodent models, excessive lipid accumulation in the myocardium causes left ventricular hypertrophy and nonischemic, dilated cardiomyopathy. Novel magnetic resonance spectroscopy techniques are now available to quantify intracellular lipid content in the myocardium and various other human tissues, which has made it possible to translate these studies into a clinical setting. By using this technology, we have recently begun to study the role of myocardial steatosis in the development of obesity-specific cardiomyopathy in humans. Recent studies in healthy individuals and patients with heart failure reveal that myocardial lipid content increases with the degree of adiposity and may contribute to the adverse structural and functional cardiac adaptations seen in obese persons. These studies parallel the observations in obese animals and provide evidence that myocardial lipid content may be a biomarker and putative therapeutic target for cardiac disease in obese patients.


Available from: Lidia S Szczepaniak, Jun 06, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dunnigan type Familial Partial Lipodystrophy (FPLD) is characterized by loss of subcutaneous fat from the limbs and excessive accumulation on the visceral adipose tissue (VAT). Affected individuals have insulin resistance (IR), diabetes, dyslipidemia and early cardiovascular (CV) events, due to their imbalanced distribution of total body fat (TBF). Epicardial adipose tissue (EAT) is correlated with VAT. Hence, EAT could be a new index of cardiac and visceral adiposity with great potential as a marker of CV risk in FPLD. Compare EAT in FPLD patients versus healthy controls. Moreover, we aimed to verify if EFT is related to anthropometrical (ATPM) and Dual-Energy X-ray Absorptiometry (DEXA) measures, as well as laboratory blood findings. We postulated that FPLD patients have enlarged EAT. This is an observational, cross-sectional study. Six patients with a confirmed mutation in the LMNA gene for FPLD were enrolled in the study. Six sex, age and BMI-matched healthy controls were also selected. EFT was measured by transthoracic echocardiography (ECHO). All participants had body fat distribution evaluated by ATPM and by DEXA measures. Fasting blood samples were obtained for biochemical profiles and also for leptin measurements. Median EFT was significantly higher in the FPLD group than in matched controls (6.0 ± 3.6 mm vs. 0.0 ± 2.04 mm; p = 0.0306). Additionally, FPLD patients had lower leptin values. There was no significant correlation between EAT and ATPM and DEXA measurements, nor laboratory findings. This study demonstrates, for the first time, that EAT measured by ECHO is increased in FPLD patients, compared to healthy controls. However, it failed to prove a significant relation neither between EAT and DEXA, ATPM or laboratory variables analyzed.
    Diabetology and Metabolic Syndrome 04/2015; 7(1):29. DOI:10.1186/s13098-015-0024-5 · 2.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Left ventricular (LV) hypertrophy increases the risk of future cardiovascular events. The relationship between obesity in young adulthood and later LV geometry is unknown. We examined the association between long-term changes in measures of adiposity and subsequent LV geometry among 1073 young adults from the Bogalusa Heart Study. Echocardiography-measured LV geometry was classified into normal (N = 796), concentric remodeling (N = 124), eccentric hypertrophy (N = 99), and concentric hypertrophy (N = 54) by integrating relative wall thickness and LV mass index. The mean age of our population was 38 years when the LV geometry was measured. Body mass index (BMI) increased by a mean of 4.9 kg/m(2) over a median of 20 years, waist circumference (WC) by 10.9 cm over 17 years, waist/hip ratio by 0.02 over 10 years, waist/height ratio by 0.06 over 17 years, abdominal height by 0.9 cm over 10 years, body fat (BF) percentage by 12.7% over 20 years, and Visceral Adiposity Index by 0.30 over 17 years. In polytomous logistic regression models corrected for multiple comparisons, participants with one-standard-deviation increases in BMI, WC, waist/height ratio, and BF had 2.00 (95% confidence interval (CI): 1.53-2.61), 1.33 (1.06-1.68), 1.35 (1.07-1.70), and 1.60 (1.26-2.03) times the risk of eccentric hypertrophy, respectively, after adjustment for demographic, lifestyle, metabolic risk factors, and follow-up time. Likewise, the rates of change in BMI, WC, waist/height ratio, and BF were associated with eccentric hypertrophy. There was no association with concentric remodeling or concentric hypertrophy. Our findings suggest that increases in BMI, WC, waist/height ratio, and BF were strong predictors of eccentric hypertrophy in middle age. Copyright © 2014 Elsevier B.V. All rights reserved.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2014; 25(3). DOI:10.1016/j.numecd.2014.11.001 · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lipid accumulation in the heart is associated with obesity and diabetes and may play an important role in the pathogenesis of heart failure. The renin-angiotensin system is also thought to contribute to cardiovascular morbidity in obese and diabetic patients. We hypothesized that the presence of lipid within the myocyte might potentiate the cardiomyopathic effects of angiotensin II in the cardiac diacylglycerol acyl transferase 1 (DGAT1) transgenic mouse model of myocyte steatosis. Treatment with angiotensin II resulted in a similar increase in blood pressure in both nontransgenic and DGAT1 transgenic mice. However, angiotensin II in the DGAT1 transgenic mice resulted in a marked increase in interstitial fibrosis and a reduction in systolic function compared to nontransgenic littermates. Lipidomic analysis revealed that over 20% of lipid species were significantly altered between NTg and DGAT1 animals while 3% were responsive to angiotensin II administration. Reactive oxygen species were also increased by angiotensin II in the DGAT1 transgenic heart. Angiotensin II treatment resulted in increased expression of transforming growth factor beta 2 (TGFβ2) and the type I TGFβ receptor, as well as increased phosphorylation of SMAD2 in the DGAT1 transgenic heart. Injection of neutralizing antibodies to TGFβ resulted in a reduction in fibrosis in the DGAT1 transgenic hearts treated with angiotensin II. These results suggest that myocyte steatosis amplifies the fibrotic effects of angiotensin II through mechanisms that involve activation of TGFβ signaling and increased production of reactive oxygen species. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 12/2014; 308(4):ajpheart.00742.2014. DOI:10.1152/ajpheart.00742.2014 · 4.01 Impact Factor

Similar Publications