Human epicardial adipose tissue expresses glucose-dependent insulinotropic polypeptide, glucagon, and glucagon-like peptide-1 receptors as potential targets of pleiotropic therapies.

AIMS: Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein-coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). METHODS AND RESULTS: Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). CONCLUSIONS: Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the glucagon-like peptide-1 receptor (GLP-1R) agonists.Human EAT is found to express the genes encoding the receptors of glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon receptor (GCGR), and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. Epicardial adipose tissue GIPR is inversely associated with genes involved in free fatty acid (FFA) oxidation and transport and with genes promoting FFA biosynthesis and adipogenesis. Epicardial adipose tissue GCGR is correlated with genes promoting FFA transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFA biosynthesis and adipogenesis.As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPR/GLP-1R agonists, and GLP-1R/GIPR/GCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ-specific fat depots through G-protein­coupled receptors may produce beneficial cardiovascular and metabolic effects.

The density of crown-like structures in epicardial adipose tissue could play a role in cardiovascular diseases.

PURPOSE: The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. METHODS: We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n = 5) or valvular replacement (VR) (n = 5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. RESULTS: Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/104 adipocytes vs. 0.0 CLS/104 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. CONCLUSIONS: CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain. LEVEL OF EVIDENCE: No level of evidence; this is a basic science study.

Quantification of epicardial adipose tissue in obese patients using an open-bore MR scanner.

BACKGROUND: Our aim was to evaluate the reproducibility of epicardial adipose tissue (EAT) volume, measured on scans performed using an open-bore magnetic resonance scanner. METHODS: Consecutive patients referred for bariatric surgery, aged between 18 and 65 years who agreed to undergo cardiac imaging (MRI), were prospectively enrolled. All those with cardiac pathology or contraindications to MRI were excluded. MRI was performed on a 1.0-T open-bore scanner, and EAT was segmented on all scans at both systolic and diastolic phase by two independent readers (R1 with four years of experience and R2 with one year). Data were reported as median and interquartile range; agreement and differences were appraised with Bland-Altman analyses and Wilcoxon tests, respectively. RESULTS: Fourteen patients, 11 females (79%) aged 44 (41-50) years, underwent cardiac MRI. For the first and second readings, respectively, EAT volume was 86 (78-95) cm3 and 85 (79-91) cm3 at systole and 82 (74-95) cm3 and 81 (75-94) cm3 at diastole for R1, and 89 (79-99) cm3 and 93 (84-98) cm3 at systole and 92 (85-103) cm3 and 93 (82-94) cm3 at diastole for R2. R1 had the best reproducibility at diastole (bias 0.3 cm3, standard deviation of the differences (SD) 3.3 cm3). R2 had the worst reproducibility at diastole (bias 3.9 cm3, SD 12.1 cm3). The only significant difference between systole and diastole was at the first reading by R1 (p = 0.016). The greatest bias was that of inter-reader reproducibility at diastole (-9.4 cm3). CONCLUSIONS: Reproducibility was within clinically acceptable limits in most instances.

Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-determination: the Italian Road to Bariatric Surgery.

PURPOSE: Bariatric surgery (BS) is considered the most efficient treatment for severe obesity. International guidelines recommend multidisciplinary approach to BS (general practitioners, endocrinologists, surgeons, psychologists, or psychiatrists), and access to BS should be the final part of a protocol of treatment of obesity. However, there are indications that general practitioners (GPs) are not fully aware of the possible benefits of BS, that specialty physicians are reluctant to refer their patients to surgeons, and that patients with obesity choose self-management of their own obesity, including internet-based choices. There are no data on the pathways chosen by physicians and patients to undergo BS in the real world in Italy. METHODS: An exploratory exam was performed for 6 months in three pilot regions (Lombardy, Lazio, Campania) in twenty-three tertiary centers for the treatment of morbid obesity, to describe the real pathways to BS in Italy. RESULTS: Charts of 2686 patients (788 men and 1895 women, 75.5% in the age range 30-59 years) were evaluated by physicians and surgeons of the participating centers. A chronic condition of obesity was evident for the majority of patients, as indicated by duration of obesity, by presence of several associated medical problems, and by frequency of previous dietary attempts to weight loss. The vast majority (75.8%) patients were self-presenting or referred by bariatric surgeons, 24.2% patients referred by GPs and other specialists. Self-presenting patients were younger, more educated, more professional, and more mobile than patients referred by other physicians. Patients above the age of 40 years or with a duration of obesity greater than 10 years had a higher prevalence of all associated medical problems. CONCLUSIONS: The majority of patients referred to a tertiary center for the treatment of morbid obesity have a valid indication for BS. Most patients self-refer to the centers, with a minority referred by a GP or by specialists. Self-presenting patients are younger, more educated, more professional, and more mobile than patients referred by other physicians. Older patients and with a longer duration of obesity are probably representative of the conservative approach to BS, often regarded as the last resort in an endless story.

Abdominal obesity phenotype is associated with COVID-19 chest X-ray severity score better than BMI-based obesity.

PURPOSE: Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. METHODS: This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. RESULTS: Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P < 0.001; P = 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P = 0.104; P = 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r = 0.43, P < 0.001; r = 0.41, P < 0.001; r = 0.17, P = 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60-0.75] and 0.67 [0.60-0.74] vs 0.58 [0.51-0.66], P = 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25-2.45, P < 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07-2.81, P = 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94-0.97, P < 0.001) as the only independent factors associated with high CXR severity scores. CONCLUSION: Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely. Level of evidence Cross-sectional descriptive study, Level V.

Antibody responses to BNT162b2 mRNA vaccine: Infection-naïve individuals with abdominal obesity warrant attention.

OBJECTIVE: The excess of visceral adipose tissue might hinder and delay immune response. How people with abdominal obesity (AO) will respond to mRNA vaccines against SARS-CoV-2 is yet to be established. SARS-CoV-2-specific antibody responses were evaluated after the first and second dose of the BNT162b2 mRNA vaccine, comparing the response of individuals with AO with the response of those without, and discerning between individuals with or without prior infection. METHODS: Immunoglobulin G (IgG)-neutralizing antibodies against the Trimeric complex (IgG-TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose 1, and at 1 and 3 months after dose 2. Nucleocapsid antibodies were assessed to detect prior SARS-CoV-2 infection. Waist circumference was measured to determine AO. RESULTS: Between the first and third month after vaccine dose 2, the drop in IgG-TrimericS levels was more remarkable in individuals with AO compared with those without AO (2.44-fold [95% CI: 2.22-2.63] vs. 1.82-fold [95% CI: 1.69-1.92], respectively, p < 0.001). Multivariable linear regression confirmed this result after inclusion of assessed confounders (p < 0.001). CONCLUSIONS: The waning antibody levels in individuals with AO may further support recent recommendations to offer booster vaccines to adults with high-risk medical conditions, including obesity, and particularly to those with a more prevalent AO phenotype.

Epicardial fat inflammation response to COVID-19 therapies.

OBJECTIVE: Adipose tissue plays a role in the novel coronavirus disease 2019 (COVID-19). Epicardial adipose tissue (EAT), a unique visceral fat, presents with a high degree of inflammation in severe COVID-19. Whether and how adipose tissue may respond to the COVID-19 therapies is unknown. METHODS: The difference in computed tomography-measured EAT and subcutaneous (SAT) attenuation, defined as mean attenuation expressed in Hounsfield units (HU), was retrospectively analyzed in 72 patients (mean [SD] age was 59.6 [12.4] years, 50 patients [69%] were men) at the hospital admission for COVID-19 and 99 days (interquartile range = 71-129) after discharge. RESULTS: At the admission, EAT-HU was significantly correlated with blood glucose levels, interleukin 6, troponin T levels, and waist circumference. EAT-HU decreased from -87.21 (16.18) to -100.0 (11) (p < 0.001), whereas SAT-HU did not change (-110.21 [12.1] to -111.11 [27.82]; p = 0.78) after therapy. Changes in EAT-HU (expressed as ∆) significantly correlated with dexamethasone therapy (r = -0.46, p = 0.006) and when dexamethasone was combined with tocilizumab (r = -0.24, p = 0.04). CONCLUSIONS: Dexamethasone therapy was associated with significant reduction of EAT inflammation in COVID-19 patients, whereas SAT showed no changes. Anti-inflammatory therapies targeting visceral fat may be helpful in COVID-19.

Tri-Ponderal Mass Index vs body Mass Index in discriminating central obesity and hypertension in adolescents with overweight.

BACKGROUND AND AIMS: Recently, it has been hypothesized that Tri-Ponderal Mass Index (TMI) may be a valid alternative to Body Mass Index (BMI) when measuring body fat in adolescents. We aimed to verify whether TMI has better accuracy than BMI in discriminating central obesity and hypertension in adolescents with overweight. METHODS AND RESULTS: This monocentric and retrospective cross-sectional study included 3749 pupils, 1889 males and 1860 females, aged 12-13. BMI (kg/m2) was calculated and expressed as percentiles and as z-scores. TMI (kg/m3) was calculated, and we used pre-defined cut-off previously proposed by Peterson et al.. For central obesity we adopted the Waist-to-Height Ratio (WHtR) discriminatory value of 0.5. Hypertension was defined as blood pressure ≥95th percentile of age- sex-, and height-specific references recommended by NHBPEP Working Group. The discriminant ability of TMI, BMI and BMI z-score, with respect to central obesity and hypertension, was investigated using non-parametric receiver operating characteristic analysis. The overall misclassification rate for central obesity was 8.88% for TMI vs 14.10% for BMI percentiles and vs 14.92% for BMI z-scores (P < 0.001). The overall misclassification rate for hypertension was 7.50% for TMI vs 22.03% for BMI percentiles and vs 25.19% for BMI z-scores (P < 0.001). CONCLUSION: TMI is a superior body fat index and it could discriminate body fat distribution more accurately than BMI. This supports the use of TMI, in association with WHtR, to characterize adolescents with overweight and high cardio-metabolic risk. Our analysis needs to be extended to other ethnic groups and replicated in a wider age range and in longitudinal studies.

Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women.

PURPOSE: Soluble receptor for advanced glycation end products (sRAGE) is a decoy receptor which sequesters RAGE ligands and acts as a cytoprotective agent. To date, it is unclear whether the lower sRAGE levels observed in obesity are a marker of increased overall adiposity or reflect increases in particular fat depots. Therefore, we evaluated in healthy women the relationship among sRAGE and indicators of adiposity, including abdominal visceral (VAT) and epicardial visceral (EAT) adipose tissues, to explore the potential role of sRAGE as an earlier biomarker of cardiometabolic risk. METHODS: Plasma sRAGE levels were quantified by an enzyme-linked immunosorbent assay in 47 healthy women. Total fat mass (FM) and fat-free mass were estimated with bioimpedance analysis. Anthropometric measures and biochemical data were recorded. Subcutaneous adipose tissue, VAT and EAT volumes were measured by magnetic resonance imaging. RESULTS: Obese women had lower sRAGE levels compared to normal-weight women. sRAGE levels were also lower in women with a waist circumference (WC) larger than 80 cm. Correlation analyses indicated an inverse association of sRAGE with body mass index and FM. Concerning adipose tissue distribution, sRAGE inversely correlated with WC, EAT and VAT depots. In a multiple stepwise regression analysis, performed to emphasize the role of fat distribution, EAT volume was the only predictor of sRAGE. CONCLUSIONS: Lower sRAGE levels reflect accumulation of visceral fat mainly at the epicardial level and are present in advance of metabolic complications in adult women. sRAGE quantification might be an early marker of cardiometabolic risk.

Association between a school-based intervention and adiposity outcomes in adolescents: The Italian "EAT" project.

OBJECTIVE: To evaluate whether a school-based multicomponent educational program could improve adiposity measures in middle-school adolescents. METHODS: A non-randomized controlled pilot study was conducted in six state middle schools (487 adolescents, 11-15 years) in townships in an urban area around Milan, three schools (n = 262 adolescents) being assigned to the intervention group and three schools (n = 225 adolescents) to the control group. The two-school-year intervention included changes in the school environment (alternative healthy vending machines, educational posters) and individual reinforcement tools (school lessons, textbook, text messages, pedometers, re-usable water bottles). The main outcome measure was change in BMI z-score. The secondary outcomes were changes in waist-to-height ratio (WHtR) and behavioral habits. RESULTS: The intervention was associated with a significant difference in BMI z-score (-0.18 ± 0.03, P<0.01) and in WHtR (-0.04 ± 0.002, P < 0.001), after controlling for baseline covariates. Subgroup analysis showed the maximum association between the intervention and the difference in BMI z-score for girls with overweight/obesity. Physical activity increased and consumption of sugar-sweetened beverages and high-energy snacks decreased in adolescents after the intervention. CONCLUSIONS: A school-based multicomponent intervention conducted at both environmental and individual levels may be effective for reducing adiposity measures mainly in adolescents with overweight/obesity.

Effect of an isocaloric diet containing fiber-enriched flour on anthropometric and biochemical parameters in healthy non-obese non-diabetic subjects.

We studied the effect of soluble fiber-enriched products on anthropometric and biochemical variables in 30 healthy non-obese, non-diabetic subjects. This was a randomized, controlled crossover, single-blind, dietary intervention study performed for 8 weeks. Subjects received an isocaloric diet with fiber-enriched products for the first 4 weeks and with regular flour products for the following 4 weeks, or vice versa. Weight, height, measures of fat distribution (waist, hip circumference), glucose, insulin and triglycerides were measured at baseline, after 4 and 8 weeks of intervention. BMI and insulin sensitivity indices were calculated. Weight and BMI decreased in the first period of isocaloric diet in both groups, regardless of the type of flour consumed (weight p<0.01, p<0.001 respectively; BMI p = 0.01, p<0.001 respectively). At the end of the 8 weeks, weight and BMI further decreased in the group consuming the fiber-enriched diet (p<0.01). Insulin resistance, estimated with the Homeostasis Model Assessment index and the Lipid Accumulation Product index, improved in all subjects after the fiber-enriched flour diet (p = 0.03, p = 0.02, respectively). In conclusion, an isocaloric diet supplemented with fiber-enriched products may improve measures of fatness and insulin sensitivity in healthy non-obese non-diabetic subjects. We might hypothesize a similar effect also in subjects with metabolic abnormalities.

The "lipid accumulation product" is associated with 2-hour postload glucose outcomes in overweight/obese subjects with nondiabetic fasting glucose.

"Lipid accumulation product" (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18-70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m(2)) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P = 0.006 and P = 0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

Relation of echocardiographic epicardial fat thickness and myocardial fat.

Epicardial and myocardial fats increase with degree of visceral adiposity and possibly contribute to obesity-associated cardiac changes. Echocardiographic epicardial fat thickness is a new and independent marker of visceral adiposity. The aim of this study was to test whether echocardiographic epicardial fat is related to myocardial fat. Twenty consecutive Caucasian men (body mass index 30.5 +/- 2 kg/m(2), 42 +/- 7 years of age) underwent transthoracic echocardiography for epicardial fat thickness, morphologic and diastolic parameter measurements, hydrogen-1 magnetic resonance spectroscopy for myocardial fat quantification, and magnetic resonance imaging for epicardial fat volume estimation. Hydrogen-1 magnetic resonance spectroscopic myocardial fat content, magnetic resonance imaging of epicardial fat volume, and echocardiographic epicardial fat thickness range varied from 0.5% to 31%, 4.5 to 43 ml, and 3 to 15 mm, respectively. Myocardial fat content showed a statistically significant correlation with echocardiographic epicardial fat thickness (r = 0.79, p <0.01), waist circumference (r = 0.64, p <0.01), low-density lipoprotein cholesterol (r = 0.54, p <0.01), plasma adiponectin levels (r = -0.49, p <0.01), and isovolumic relaxation time (r = 0.59, p <0.01). However, multivariate linear regression analysis showed epicardial fat thickness as the most significant independent correlate of myocardial fat (p <0.001). Although this study is purely correlative and no causative conclusions can be drawn, it can be postulated that increased echocardiographic epicardial fat accumulation could reflect myocardial fat in subjects with a wide range of adiposity.

Epicardial fat thickness: relationship with plasma visfatin and plasminogen activator inhibitor-1 levels in visceral obesity.

BACKGROUND AND AIM: Epicardial fat (EF), a true visceral adipose tissue (VAT) deposited around the heart, is considered as possible cardiovascular risk indicator, in view of its ability to produce and release several inflammatory adipo-cytokines. It is still not known whether increased cardiac adiposity is related to increased inflammatory adipo-cytokines in obesity. The aim of this study was to evaluate whether echocardiographic EF thickness, an indicator of cardiac adiposity, is related to circulating levels of inflammatory adipo-cytokines such as visfatin and plasminogen activator inhibitor-1 (PAI-1) in visceral obesity. METHODS AND RESULTS: EF thickness (measured by echocardiography), visfatin, PAI-1 antigen and some inflammatory markers were studied in 42 women, 27 of them severely obese (OB) (BMI 43.5+/-4.8 kg/m(2)) but with no apparent complications, and 15 normal-weight controls. Abdominal VAT in the OB was assessed by computed tomography. OB had thicker EF and higher visfatin and PAI-1 antigen concentrations than controls (P<0.0001). EF thickness, log-visfatin and log-PAI-1 antigen concentrations directly correlated with VAT (P<0.0001). Log-visfatin and log-PAI-1 antigen were correlated with EF thickness even after adjusting for indices of fat distribution (P<0.01 and P<0.001 respectively). Moreover, when dividing OB on the basis of median EF thickness, women with greater EF thickness had more VAT and higher adipo-cytokine concentrations and inflammatory markers. CONCLUSIONS: This study suggests that EF thickness, an indicator of cardiac adiposity, may be significantly related to inflammatory adipo-cytokines in visceral-obese patients. This suggests EF might be used as an easy and reliable marker of visceral adiposity and inflammation and as a cardiovascular risk indicator.

Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity: relationship with abdominal fat deposition.

BACKGROUND AND AIM: Obesity can be considered a state of chronic, low-grade inflammation. Particularly, visceral adipose tissue (VAT) seems to be an active compartment in pro-inflammatory molecule secretion. The possible existence of a correlation between circulating cytokines, their soluble receptors, abdominal fat accumulation and echocardiographic abnormalities in uncomplicated obesity was investigated. METHODS AND RESULTS: Echocardiographic parameters, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6-R), tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptor I (TNFR-I) were assessed in 27 normotensive obese women (age 33.3+/-8.3 years; BMI 43.5+/-4.8 kg/m2) and 15 normal-weight controls (age 36.8+/-8.2 years; BMI 22.6+/-1.7 kg/m2). VAT was assessed by CT. The obese patients had higher serum IL-6 (p<0.01), sIL-6-R (p<0.0001), sIL-6-R/IL-6 complex (p<0.05), TNF-alpha (p<0.02), sTNF-alpha-RI (p<0.03) and CRP (p<0.0001) levels than normal women. Moreover, end-diastolic septum thickness (SW), end-diastolic posterior wall thickness (PW), absolute and indexed left ventricular mass, deceleration time (DT), myocardial performance index (MPI) and isovolumetric relaxation time (IVRT) were correlated with sIL-6-R, sIL-6-R/IL-6 complex and CRP levels. Interestingly, sIL-6-R, sIL-6-R/IL-6 complex, CRP, SW, PW, DT and MPI were higher in patients with a VAT area >130 cm2 than those with <130 cm2. CONCLUSION: In normotensive obese women several pro-inflammatory molecules correlate with both echocardiographic abnormalities and the amount of intra-abdominal fat; these results may support a role for visceral fat in predisposing to cardiac dysfunction, possibly through a low-grade state of inflammation.