Adiposity of the Heart*, Revisited

University of Texas Southwestern Medical Center, Dallas, Texas 75390-8899, USA.
Annals of internal medicine (Impact Factor: 17.81). 05/2006; 144(7):517-24.
Source: PubMed


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.

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Available from: Lidia S Szczepaniak, Oct 06, 2015
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    • "Fat is a scarcely elastic tissue [62] [63] and infiltration into the myocardium has to alter the tissue elastic properties, likely impairing distensibility and limiting LV dilatation. Cytosolic accumulation of fatty acid increases the size of cardiomyocytes independently of expression of sarcomeres [30] [64] and, possibly, reduces cell elastance. In addition to promoting reactive fibrosis, overproduction of cytokines from the visceral adipose tissue, namely from the IL6 family, may also contribute to sarcomeric growth in both serial and parallel directions [65e67]. "
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    ABSTRACT: Obesity is characterized by the disproportionate growth of the components of body size, including adipose tissue and lean body mass. Left ventricular (LV) hypertrophy often develops, due to the coexistence of hemodynamic (cardiac workload) and non-hemodynamic components (including body composition and activity of visceral fat). While the hypertrophy of cardiomyocytes is produced by the hemodynamic load, through sarcomeric replication, there is a parallel growth of non-muscular myocardial components, including interstitial fat infiltration and accumulation of triglycerides in the contractile elements, which are thought to influence LV geometric pattern. Thus, pure intervention on hemodynamic load is unlikely to result in effective reduction of LV hypertrophy in obese. We review pathophysiology and prevalence of LV hypertrophy in obesity, with specific attention to LV geometric abnormalities and relations with body size.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 10/2013; 23(10). DOI:10.1016/j.numecd.2013.06.012 · 3.32 Impact Factor
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    • "Dynamic cine images were used to quantify left ventricular (LV) volume [16,18,19]. Image analysis was performed by an observer blinded to the subject’s clinical history and treatment, using a commercially available workstation (MASS, Philips Medical Systems). "
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    ABSTRACT: The landmark Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) placed a new spotlight on thiazide diuretics as the first-line therapy for hypertension. This is concerning as thiazide-diuretics may contribute to comorbidities associated with the current epidemic of obesity. Previous randomized clinical trials have linked thiazide diuretic treatment to insulin resistance, metabolic syndrome, and increased incidence of type 2 diabetes. This proof of concept, longitudinal, randomized, double--blind study evaluated the effects of the angiotensin II receptor blocker Valsartan and the specific thiazide diuretic Hydrochlorothiazide (HCTZ) on hepatic triglyceride level (primary outcome), as well as triglyceride levels within other organs including the heart, skeletal muscle, and pancreas. Additionally, we evaluated whether myocardial function, insulin sensitivity, and insulin secretion were affected by these treatments. Hepatic TG levels increased by 57% post HCTZ treatment: DeltahTG HCTZ = 4.12% and remained unchanged post Valsartan treatment: DeltahTG V = 0.06%. The elevation of hepatic TG levels after HCTZ treatment was additionally accompanied by a reduction in insulin sensitivity: DeltaSI HCTZ = -1.14. Treatment with Valsartan resulted in improved insulin sensitivity: DeltaSI V = 1.24. Treatment-induced changes in hepatic TG levels and insulin sensitivity were statistically significant between groups (phTG = 0.0098 and pSI = 0.0345 respectively). Disposition index, DI, remained unchanged after HCTZ treatment: DeltaDI HCTZ = -141 but it was increased by a factor of 2 after treatment with Valsartan: DeltaDI V =1018). However, the change between groups was not statistically significant. Both therapies did not modify abdominal visceral and subcutaneous fat mass as well as myocardial structure and function. Additionally, myocardial, pancreatic, and skeletal muscle triglyceride deposits remained unchanged in both therapeutic arms. Our findings are two-fold and relate to hepatic steatosis and insulin sensitivity. HCTZ treatment worsened hepatic steatosis measured as hepatic triglyceride content and reduced insulin sensitivity. Valsartan treatment did not affect hepatic triglyceride levels and improved insulin sensitivity. The results of this study reinforce the message that in patients at risk for type 2 diabetes it is particularly important to choose an antihypertensive regimen that lowers blood pressure without exacerbating patient's metabolic profile.
    Diabetology and Metabolic Syndrome 07/2013; 5(1):35. DOI:10.1186/1758-5996-5-35 · 2.17 Impact Factor
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    • "Ectopic lipid deposition in nonadipose tissues is associated with an overstrain of the cellular oxidation capacity. This overstrain leads to insufficient substrate utilization and, consequently, to accumulation of toxic by-products that induce cell damage and organ dysfunction, specifically lipotoxicity (6). However, the precise role of cardiac steatosis in the pathogenesis of myocardial dysfunction remains unclear as yet. "
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    ABSTRACT: Increased myocardial lipid content (MYCL) recently has been linked to the development of cardiomyopathy in diabetes. In contrast to steatosis in skeletal muscle and liver, previous investigations could not confirm a link between MYCL and insulin resistance. Thus, we hypothesized that cardiac steatosis might develop against the background of the metabolic environment typical for prediabetes and early type 2 diabetes: combined hyperglycemia and hyperinsulinemia. Therefore, we aimed to prove the principle that acute hyperglycemia (during a 6-h clamp) affects MYCL and function (assessed by (1)H magnetic resonance spectroscopy and imaging) in healthy subjects (female subjects: n = 8, male subjects: n = 10; aged 28 ± 5 years; BMI 22.4 ± 2.6 kg/m(2)). Combined hyperglycemia (202.0 ± 10.6 mg/dL) and hyperinsulinemia (110.6 ± 59.0 μU/mL) were, despite insulin-mediated suppression of free fatty acids, associated with a 34.4% increase in MYCL (baseline: 0.20 ± 0.17%, clamp: 0.26 ± 0.22% of water signal; P = 0.0009), which was positively correlated with the area under the curve of insulin (R = 0.59, P = 0.009) and C-peptide (R = 0.81, P < 0.0001) during the clamp. Furthermore, an increase in ejection fraction (P < 0.0001) and a decrease in end-systolic volume (P = 0.0002) were observed, which also were correlated with hyperinsulinemia. Based on our findings, we conclude that combined hyperglycemia and hyperinsulinemia induce short-term myocardial lipid accumulation and alterations in myocardial function in normal subjects, indicating that these alterations might be directly responsible for cardiac steatosis in metabolic diseases.
    Diabetes 03/2012; 61(5):1210-6. DOI:10.2337/db11-1275 · 8.10 Impact Factor
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