Relation of body fat distribution in men and degree of coronary narrowings in coronary artery disease.

This study evaluates the relation between body fat distribution and severity of coronary artery disease (CAD). The study sample comprised 33 patients with angiographically demonstrated CAD and 10 angiographically normal control subjects. Body fat distribution was estimated by computed tomography and degree of coronary narrowings by angiographic score. Body weight, body mass index and total and subcutaneous abdominal adipose tissue areas showed no statistical differences in the 2 groups; visceral abdominal adipose tissue area and the visceral to subcutaneous abdominal adipose tissue area ratio were significantly higher in patients with CAD (p < 0.05). There was a significant correlation between visceral fat and triglycerides, apoprotein B and sum of glucose and insulin during glucose oral tolerance test. Sum of insulin during glucose oral tolerance test, visceral abdominal adipose tissue area and visceral/subcutaneous abdominal adipose tissue area ratio correlated significantly with severity of CAD, as evaluated by coronary score in all subjects and in CAD patients alone. Stepwise multiple regression analysis using the coronary score as the dependent variable and anthropometric and metabolic parameters as independent variables shows that in all subjects and in CAD patients alone, visceral/subcutaneous abdominal adipose-tissue area ratio entered the regression first and the sum of insulin during glucose oral tolerance test second. The results suggest that visceral abdominal adipose tissue area and visceral to subcutaneous abdominal adipose tissue area ratio may be cardiovascular risk factors.     

Cardiac 64-multislice computed tomography reveals increased epicardial fat volume in patients with acute coronary syndrome

Inflammatory cytokines released from epicardial fat around coronary arteries may modulate the coronary arteries and promote coronary atherosclerosis. We assessed the hypothesis that epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS). EFV was measured in 80 Japanese patients hospitalized for ACS using 64-multislice computed tomography. The ACS group included 51 patients with ST-segment elevated myocardial infarction and 29 patients with non-ST-segment elevated myocardial infarction. All patients underwent emergency coronary angioplasty and 64-multislice computed tomographic scanning during hospitalization. The control group included 90 consecutive outpatients with suspected ACS whose coronary computed tomographic results were normal. EFV was larger in patients with ACS than in the control group (117 ± 47 vs 95 ± 33 ml, p <0.001). Multivariate regression analysis showed that EFV was associated with age, body mass index, and visceral fat area in the control group. However, these correlations did not appear in the ACS group. Multivariate logistic regression analysis showed that EFV >100 ml was independently associated with ACS (odds ratio 2.84, 95% confidence interval 1.17 to 6.87, p = 0.021). Receiver operator characteristic analysis determined a cut-off value of 100.3 ml with a sensitivity of 75% and a specificity of 60% for ACS (area under the curve 0.692, 95% confidence interval 0.596 to 0.777, p <0.001). Compared to subcutaneous adipose tissue, epicardial adipose tissue showed inflammatory cell infiltrates on a micrograph. In conclusion, the present study demonstrated significantly increased EFV in patients with ACS. A large amount of epicardial fat may be a risk factor for ACS.     

Expression of fat mobilizing genes in human epicardial adipose tissue

BackgroundEpicardial adipose tissue (EAT) mass correlates with Metabolic Syndrome and coronary artery disease (CAD). However, little is known about the expression of genes involved in triglyceride (TG) storage and mobilization in EAT. We therefore analyzed the expression of genes involved in fat mobilization in EAT in comparison to subcutaneous abdominal adipose tissue (AAT) in CAD patients and in controls.MethodsEAT and AAT were obtained during coronary artery bypass graft (CABG) surgery from 16 CAD patients and from 14 non-CAD patients presenting for valve surgery. The state of atherosclerosis was assessed by angiography. RNA from tissues were extracted, reversibly transcribed and quantified by real time polymerase chain reaction (RT-PCR). The following genes were analyzed: perilipin-1 and -5 (PLIN1, PLIN5), lipoprotein lipase (LPL), hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CIG-58), angiopoietin like protein 4 (ANGPTL4), in addition to interleukine-6 (IL-6), leptin (LEP) and adiponectin (ADPN).ResultsA significant expression of all listed genes could be observed in EAT. The relative expression pattern of the 10 genes in EAT was comparable to the expression in AAT, yet there was a significantly higher overall expression in AAT. The expression of the listed genes was not different between CAD patients and controls.ConclusionIt is suggested that the postulated difference in EAT volume between CAD patients and non-CAD patients is not caused by a differential mRNA expression of fat mobilizing genes. Further work on protein levels and enzyme activities will be necessary to get a complete picture.     

Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart

A growing amount of evidence suggests that regional fat distribution plays an important part in the development of an unfavorable metabolic and cardiovascular risk profile. Epicardial fat is a metabolically active organ that generates various bioactive molecules, which might significantly affect cardiac function. This small, visceral fat depot is now recognized as a rich source of free fatty acids and a number of bioactive molecules, such as adiponectin, resistin and inflammatory cytokines, which could affect the coronary artery response. The observed increases in concentrations of inflammatory factors in patients who have undergone coronary artery bypass grafting remain to be confirmed in healthy individuals. Furthermore, epicardial adipose mass might reflect intra-abdominal visceral fat. Therefore, we propose that echocardiographic assessment of this tissue could serve as a reliable marker of visceral adiposity. Epicardial adipose tissue is also clinically related to left ventricular mass and other features of the metabolic syndrome, such as concentrations of LDL cholesterol, fasting insulin and adiponectin, and arterial blood pressure. Echocardiographic assessment of epicardial fat could be a simple and practical tool for cardiovascular risk stratification in clinical practice and research. In this paper, we briefly review the rapidly emerging evidence pointing to a specific role of epicardial adipose tissue both as a cardiac risk marker and as a potentially active player in the development of cardiac pathology.     

Human epicardial adipose tissue: a review

We discuss the anatomy, physiology, and pathophysiology of epicardial adipose tissue and its relationship to coronary atherosclerosis. Epicardial fat stores triglyceride to supply free fatty acids for myocardial energy production and produces adipokines. It shares a common embryological origin with mesenteric and omental fat. Like visceral abdominal fat, epicardial fat thickness, measured by echocardiography, is increased in obesity. Epicardial fat could influence coronary atherogenesis and myocardial function because there is no fibrous fascial layer to impede diffusion of free fatty acids and adipokines between it and the underlying vessel wall as well as the myocardium. Segments of coronary arteries lacking epicardial fat or separated from it by a bridge of myocardial tissue are protected against the development of atherosclerosis in those segments. However, when epicardial fat is totally absent in congenital generalized lipodystrophy, coronary atherosclerosis can still occur. Macrophages are more numerous and densely packed in the periadventitial fat of human atherosclerotic coronary arteries with lipid cores than in that of fibrocalcific or nonatherosclerotic coronary arteries. In obese patients with multiple cardiovascular risk factors, epicardial fat around atheromatous coronaries secretes several proinflammatory cytokines and is infiltrated by macrophages, lymphocytes, and basophils. Epicardial adipokine expression in obesity without coronary atherosclerosis has not been determined. In nonobese patients, epicardial fat around atheromatous coronary arteries expresses proinflammatory cytokines but produces either less adiponectin, a vasoprotective adipokine, than fat around nonatheromatous coronaries or a similar amount compared with thoracic subcutaneous fat. Further studies should be done to test the hypothesis that adipokines produced by and released from human epicardial adipose tissue might contribute locally to the pathogenesis of coronary atherosclerosis.     

A pilot-controlled study of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) in the coronary circulation

Hereby we report our observations derived from a pilot-study of 39 subjects (30 patients with coronary artery disease [CAD] and 9 non-CAD controls). In this work, we aimed to evaluate MPO-ANCA titer in the human coronary circulation for the first time; and examine its possible association with CAD and some cytokines/inflammatory markers. We found higher mean coronary MPO-ANCA titer in CAD subjects than in non-CAD controls; beside significant positive correlations between MPO-ANCA titers and both C-reactive protein and interleukin-6 levels. Thus, we might suggest the possible involvement of MPO-ANCA in coronary atherogenesis indirectly through modulating some pro-inflammatory cytokines/markers; that a large-scale study of MPO-ANCA in CAD patients may be warranted in the future.     

The number and phenotype of myocardial and adipose tissue CD68+ cells is associated with cardiovascular and metabolic disease in heart surgery patients

Background and aimsCD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM.Methods and resultsSamples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm²; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm²; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm²; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024).ConclusionsRegional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.     

Clinical significance of epicardial fat measured using cardiac multislice computed tomography

Cardiac adiposity defined as increased epicardial adipose tissue and massive deposits of fat within the atrial septum (lipomatous hypertrophy) is seen in overweight persons and is associated with coronary artery disease (CAD), atrial arrhythmias, and increased risk of left ventricular free wall rupture after acute myocardial infarction. Unlike subcutaneous fat, epicardial fat is metabollically active and produces hormones, cytokines, and other vasoactive substances that work systemically or locally to alter vascular endothelial function and may be implicated in the pathogenesis of CAD. The aim of the study was to assess the feasibility of measuring epicardial fat volume (EFV) and identify its clinical correlates using (64-slice) multislice computed tomography (MSCT). A protocol was devised to measure EFV using MSCT in 151 adults (age 26 to 83 years, mean 51 +/- 12; 55% men). Cross-sectional tomographic cardiac slices (2.5-mm thick) from base to apex (range 28 to 40 per heart) were traced semiautomatically using an off-line workstation, and EFV was measured by assigning Hounsfield units ranging from -30 to -250 to fat. Coronary computed tomographic angiography was performed using a standard protocol. EFV ranged from 25 to 274 ml (mean 121 +/- 47), corresponding to 2.4% to 30.5% (mean 15 +/- 5%) of total cardiac volume and correlated with age, atrial septum thickness, body weight, and body mass index. Coronary calcium score was significantly higher in patients with EFV >100 ml (67 +/- 155 vs 216 +/- 639; p = 0.03), and a higher percentage of patients with increased EFV had CAD (46% vs 31%; p <0.05) or metabolic syndrome (44% vs 29%; p <0.05). In conclusion, quantification of EFV was feasible using MSCT. Large deposits of fat around the heart and within the atrial septum were associated with obesity, coronary calcium, metabolic syndrome, and CAD. Measurement of EFV may provide another useful noninvasive indicator of heightened risk of CAD in addition to calcium score and coronary angiography.     

Human epicardial adipokine messenger RNAs: comparisons of their expression in substernal, subcutaneous, and omental fat

We compared the gene expression of inflammatory and other proteins by real-time quantitative polymerase chain reaction in epicardial, substernal (mediastinal) and subcutaneous sternal, upper abdominal, and leg fat from coronary bypass patients and omental (visceral) fat from extremely obese women undergoing bariatric surgery. We hypothesized that (1) epicardial fat would exhibit higher expression of inflammatory messenger RNAs (mRNAs) than substernal and subcutaneous fat and (2) epicardial mRNAs would be similar to those in omental fat. Epicardial fat was clearly different from substernal fat because there was a far higher expression of haptoglobin, prostaglandin D₂ synthase, nerve growth factor β, the soluble vascular endothelial growth factor receptor (FLT1), and α1 glycoprotein but not of inflammatory adipokines such as monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1β, tumor necrosis factor α, serum amyloid A, plasminogen activator inhibitor-1, or adiponectin despite underlying coronary atherosclerosis. However, the latter inflammatory adipokines as well as most other mRNAs were overexpressed in epicardial fat as compared with the subcutaneous depots except for IL-8, fatty acid binding protein 4, the angiotensin II receptor 1, IL-6, and superoxide dismutase-2. Relative to omental fat, about one third of the genes were expressed at the same levels, whereas monocyte chemoattractant protein-1, cyclooxygenase-2, plasminogen activator inhibitor-1, IL-1β, and IL-6 were expressed at far lower levels in epicardial fat. In conclusion, epicardial fat does not appear to be a potentially more important source of inflammatory adipokines than substernal mediastinal fat. Furthermore, the expression of inflammatory cytokines such as IL-6 and IL-1β is actually higher in omental fat from obese women without coronary atherosclerosis. The data do not support the hypothesis that most of the inflammatory adipokines are expressed at high levels in epicardial fat of humans.     

单核细胞/高密度脂蛋白比值与炎性脂肪因子水平及冠状动脉疾病严重程度的相关性

目的探讨单核细胞/高密度脂蛋白比值与炎性脂肪因子的相关性,并评价其对冠状动脉疾病(CAD)的辅助诊断、评估冠状动脉病变严重程度的价值。方法连续入选2017年1月至2017年8月于我院心脏内科住院,符合纳入标准的研究对象242例,依据冠状动脉造影冠状动脉主干或分支是否狭窄≥50%分为冠状动脉疾病组168例、对照组74例。收集人口学特征、临床与实验室检查资料,酶联免疫吸附法测定血清炎性脂肪因子水平。分析单核细胞/高密度脂蛋白比值与炎性脂肪因子及冠状动脉病变严重程度的相关性。并评价其对冠状动脉疾病的诊断价值。结果冠状动脉疾病组单核细胞/高密度脂蛋白比值、视黄醇结合蛋白、血五聚素3、纤溶酶原激活物抑制剂1、半乳糖凝集素3血清水平高于对照组,而白细胞介素37、神经生长因子1、脂联素血清水平低于对照组(P均0.01)。相关分析显示,单核细胞/高密度脂蛋白比值与冠状动脉Gensini评分及炎性脂肪因子存在相关性,单核细胞/高密度脂蛋白比值诊断CAD的受试者工作特征曲线下面积(ROC-AUC)为0.676。结论单核细胞/高密度脂蛋白比值升高、炎性脂肪因子水平改变可作为辅助诊断CAD、评估冠状动脉病变严重程度的标志物。     

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women

OBJECTIVE: We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines. SUBJECTS: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated. METHOD: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay. RESULTS: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount. CONCLUSION: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.     

Influence of EPICardial adipose tissue in HEART diseases (EPICHEART) study: Protocol for a translational study in coronary atherosclerosis

IntroductionAccumulation of epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) and increased risk of coronary events in asymptomatic subjects and low-risk patients, suggesting that EAT promotes atherosclerosis in its early stage. Recent studies have shown that the presence of CAD affects the properties of adjacent EAT, leading to dynamic changes in the molecular players involved in the interplay between EAT and the coronary arteries over the history of the disease. The role of EAT in late-stage CAD has not been investigated.ObjectivesIn a comparative analysis with mediastinal and subcutaneous adipose tissue, we aim to investigate whether the volume of EAT assessed by computed tomography and its proteome assessed by SWATH-MS mass spectrometry are associated with late stages of CAD in an elderly cohort of severe aortic stenosis patients.MethodsThe EPICHEART study (NCT03280433) is a prospective study enrolling patients with severe degenerative aortic stenosis referred for elective aortic valve replacement, whose protocol includes preoperative clinical, nutritional, echocardiographic, cardiac computed tomography and invasive coronary angiographic assessments. During cardiac surgery, samples of EAT and mediastinal and subcutaneous thoracic adipose tissue are collected for proteomics analysis by SWATH-MS. In addition, pericardial fluid and peripheral and coronary sinus blood samples are collected to identify circulating and local adipose tissue-derived biomarkers of CAD.ConclusionWe designed a translational study to explore the association of EAT quantity and quality with advanced CAD. We expect to identify new biochemical factors and biomarkers in the crosstalk between EAT and the coronary arteries that are involved in the pathogenesis of late coronary atherosclerosis, especially coronary calcification, which might be translated into new therapeutic targets and imaging tools by biomedical engineering.     

1085例冠状动脉造影患者血清尿酸浓度与冠心病危险因素的相关性

目的探讨血清尿酸浓度与冠心病发生的预测价值。方法回顾性分析了1085例因胸痛接受冠状动脉造影的具有至少一个冠心病危险因素的患者,根据冠心病确诊情况分为冠心病组(574例)和非冠心病组(511例),观察血清尿酸浓度与冠心病是否存在相关性。结果冠心病组血清尿酸浓度高于非冠心病组。两组血清尿酸浓度有显著性差异(P<0.01)。多因素逐步回归显示,高尿酸血症是冠心病的独立危险因素。结论高尿酸血症是本组患者预测冠心病的一个独立的危险因素。     

Adipose tissue depot-specific differences in adipocyte apolipoprotein E expression

Important differences in gene expression have been documented in adipocytes derived from specific adipose tissue depots. We have previously documented an important role for adipocyte apolipoprotein E (apoE) in modulating adipocyte and adipose tissue triglyceride and lipoprotein metabolism. We now evaluate the endogenous expression of apoE in adipocytes isolated from unique adipose tissue depots in 4 different species. Adipocyte apoE expression is higher in subcutaneous fat compared with visceral fat in humans, mice, rats, and baboons. In baboons, evaluation of apoE expression in 5 adipose tissue depots (subcutaneous abdominal, subcutaneous gluteal, visceral, pericardial, epicardial) showed that, compared with subcutaneous abdominal adipocytes, the level of apoE expression is similar in subcutaneous gluteal, lower in visceral and pericardial, and higher in epicardial adipocytes. Consistent with previously demonstrated suppression of adipocyte apoE by adipose tissue inflammation, adipose tissue depots with lower apoE expression demonstrated greater infiltration of macrophages and an increased expression of tumor necrosis factor–α messenger RNA. Depot-specific differences in apoE expression were maintained after in vitro differentiation. Adipocytes isolated from depots with lower apoE expression manifested lower rates of triglyceride synthesis in the absence and presence of triglyceride-rich lipoproteins. Adenoviral-mediated increase of apoE expression in omental adipocytes increased triglyceride synthesis in these cells. Our results demonstrate significant heterogeneity in adipocyte apoE expression across adipose tissue depots in several species. Because of its role in modulating adipocyte triglyceride and lipoprotein metabolism, depot-specific differences in endogenous adipocyte apoE could have important implications for modulating the accumulation of lipid in these depots.     

Epicardial adipose tissue as a predictor of coronary artery disease in asymptomatic subjects

This study sought to elucidate the relation between epicardial adipose tissue (EAT) thickness measured by multidetector computed tomography and presence of coronary artery atherosclerosis. Recent studies have suggested that fat disposition in visceral organs and epicardial tissue could serve as a predictor of coronary artery disease (CAD). The sample included 190 asymptomatic subjects with ≥ 1 cardiovascular risk factor who were referred for cardiac computed tomographic angiography. Body mass index, blood pressure, fasting glucose level, and lipid profile were measured. Multidetector computed tomographic results were analyzed for atherosclerosis burden, calcium Agatston score, and EAT thickness: mean EAT values were 3.54 ± 1.59 mm in patients with atherosclerosis and 1.85 ± 1.28 mm in patients without atherosclerosis (p <0.001). On receiver operating characteristic analysis, an EAT value ≥ 2.4 mm predicted the presence of significant (>50% diameter) coronary artery stenosis. There was a significant difference in EAT values between patients with and without metabolic syndrome (2.58 ± 1.63 vs 2.04 ± 1.46 mm, p <0.05) and between patients with a calcium score >400 and <400 (3.38 ± 1.58 vs 2.02 ± 1.42 mm, p <0.0001). In conclusion, asymptomatic patients with CAD have significantly more EAT than patients without CAD. An EAT thickness of 2.4 mm is the optimal cutoff for prediction of presence of significant CAD.     

血浆脂蛋白(a)浓度与青年人群冠心病关系的横断面研究

目的:探讨血浆脂蛋白(a)[Lp(a)]浓度与青年人群冠心病的相关性。方法:选取2018年3月至2019年2月期间在中国医学科学院阜外医院行冠状动脉造影术的1 093例青年患者作为研究对象(<45岁),按照冠状动脉造影结果分为冠心病组(n=906)和非冠心病组(n=187)。采用Gensini评分法评估冠心病组患者的冠状动脉病变严重程度,并将其分为三个亚组:高Gensini评分亚组(n=302)、中Gensini评分亚组(n=302)、低Gensini评分亚组(n=302)。收集所有研究对象的病史及相关临床与实验室检测指标,血浆Lp(a)检测采用免疫比浊法;分析基线血浆Lp(a)浓度与冠心病诊断及严重程度之间的关系。结果:冠心病组患者血浆Lp(a)浓度显著高于非冠心病组[13.46(6.58~28.91)mg/dl vs 8.39(5.06~19.31)mg/dl,P<0.001]。进一步分析显示,冠心病组男性、女性、高血压、无高血压、无糖尿病患者的血浆Lp(a)浓度均显著高于非冠心病组(P均<0.05)。多因素Logistic回归分析表明,logLp(a)水平升高为青年冠心病的独立危险因素(OR=2.898,95%CI:1.949~4.311,P<0.001)。在冠心病组患者中,高Gensini评分亚组的Lp(a)浓度明显高于中Gensini评分亚组及低Gensini评分亚组[18.07(9.22~40.29)mg/dl vs13.89(6.57~32.77)mg/dl、9.63(4.83~18.96)mg/dl,P均<0.001]。多元线性回归分析表明,较高logLp(a)水平与高Gensini评分显著相关(B=0.353,P<0.001)。结论:横断面观察提示,血浆Lp(a)浓度与青年人群冠心病的发生及病变严重程度相关,其结果有待更大样本前瞻性研究证实。     

Epicardial fat: properties, function and relationship to obesity

Epicardial fat is a relatively neglected component of the heart. The purpose of this review was to examine the anatomic and biochemical data on epicardial fat; to examine the relationship of epicardial fat to obesity and to explore the potential role of epicardial fat in the relationship of obesity to coronary atherothrombotic disease. Epicardial fat covers 80% of the heart's surface and constitutes 20% of total heart weight. It is present along the distribution of the coronary arteries, over the right ventricle especially along the right border, anterior surface and at the apex. There is three- to fourfold more epicardial fat associated with the right than the left ventricle. Putative physiologic functions of epicardial fat are based on observational data and include: buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, facilitating coronary artery remodelling, regulating fatty acid homeostasis in the coronary microcirculation and providing fatty acids to cardiac muscle as a local energy source in times of high demand. A considerable amount of the data on epicardial fat originates from autopsy series that have the inherent problem that conditions leading to death may have altered body composition and adiposity. With this caveat, data indicate that epicardial fat mass increases age until age 20-40 years but thereafter the amount of epicardial fat is not dependent on age. The amount of epicardial fat correlates with heart weight but the presence of myocardial ischemia and hypertrophy does not alter the ratio of epicardial fat to cardiac muscle mass. A number of properties differentiate epicardial fat from other fat depots specifically its smaller adipocytes size; different fatty acid composition, high protein content; high rates of fatty acid incorporation, fatty acid synthesis, insulin-induced lipogenesis or fatty acid breakdown; low rates of glucose utilization, low expression (mRNA) of lipoprotein lipase, stearoyl-CoA desaturase and acetyl-CoA carboxylase-alpha, and slow regression during weight loss. There is a significant direct relationship between the amount of epicardial fat and general body adiposity. Clinical imaging studies have demonstrated a strong direct correlation between epicardial fat and abdominal visceral adiposity. Several lines of evidence support a role for epicardial fat in the pathogenesis of coronary artery disease, namely the close anatomic relationship between epicardial fat and coronary arteries; the positive correlation between the amount of epicardial fat and the presence of coronary atherosclerosis and the ability of adipose tissue to secrete hormones and cytokines that modulate coronary artery atherothrombosis. Thus, epicardial fat maybe an important factor responsible for cardiovascular disease in obesity.     

Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines

BACKGROUND: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue. METHODS: Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding. RESULTS: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue. CONCLUSIONS: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.