Pericardial Adipose Tissue Research Articles

700 EPICARDIAL ADIPOSE TISSUE AND ATRIAL FIBRILLATION, A REVIEW

Abstract Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia closely associated with stroke, heart failure, and decreased quality of life. Excess adiposity has long been associated with increased cardiovascular disease and risk factor of AF. Methods Epicardial Adipose Tissue (EAT) is the fat depot located between the myocardium and the epicardium supplied by branches of the coronary arteries. By contrast, pericardial adipose tissue (PAT) is located externally and is supplied by non-​coronary arteries. EAT fat thickness was first visualized by and measured with Transthoracic Two-dimensional (2D) Echocardiography because is visible as an echo free space between the outer wall of the myocardium and the visceral layer of the pericardium. Moreover, computed tomography (CT) has been used to measure EAT through accurate volumetric measurement. CMR imaging is instead considered the ‘gold standard’ modality for imaging adipose tissue.EAT function and morphology in normal conditions is protective but it function changes under pathological conditions.Lots of studies, infact, indicated higher pericardial fat volume was associated with a nearly 40% higher odds of prevalent AF, and the association remained significant even after adjustment for other AF risk factors including age, sex, myocardial infarction, heart failure, BMI, and other regional fat deposits. Infact, EAT volume is related to impaired diastolic function, elevated left ventricular mass, and enlarged left atrium. Moreover, a higher degree of EAT accumulation is often observed in patients with systematic inflammatory disease and oxidative stress, such as rheumatoid arthritis and psoriasis, compared with those without systematic inflammatory disease even after adjusting other risk factors. Free fatty acids can be transported from EAT to the myocardium and lead to electromechanical changes in atrial tissue: they separate cardiomyocytes and this situation result in conduction slowing, loss of side-​to-​side cell connections and myocardial disorganization that leads to conduction delay and re-​entry. Results EAT is a modifiable cardiovascular risk factor and a potential novel therapeutic target owing to its responsiveness to drugs with pleiotropic effects such as GLP1R agonists (visceral fat reduction is one of the non-​glycaemic effects of the GLP1R agonists), SGLT2 inhibitors (reduction of intramyocardial lipid content by increasing EAT lipolysis and ketone body oxidation) and statins (reduction of EAT thickness through modulation of peroxisome proliferator-​activated receptors (PPARs)). Furthemore, suppression of AF after injecting botulinum toxin into EAT in patients with paroxysmal AF, both during postoperative cardiac surgery and catheter ablation of epicardial fat pad can also result in EAT reduction. Conclusion EAT is a measurable and modifiable cardiovascular risk factor that adds qualitative value to the stratification of cardiovascular risk. In the context of atrial fibrillation, EAT represents a new pathogenic substrate through the regional secretion of factors that induce fibrosis and neurohormonal disarray of the atrial myocytes. Genetic studies are also optional to uncover pathophysiological mechanism of EAT-AF interaction and clarify causal relationship. Finally, more efforts should be made to realize application of EAT quantification in risk evaluation and management for AF.

Association of Epicardial and Pericardial Adipose Tissue Volumes with Coronary Artery Calcification.

Epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) are anatomically close to the myocardium and may influence cardiovascular pathology. Thus, in this study, we aim to assess whether EAT and PAT volumes were associated with coronary artery calcification score (CCS) in patients with suspected coronary artery disease (CAD), especially in overweight and obese individuals.We included consecutive patients with suspected CAD in whom EAT volume, PAT volume, and CCS were measured via computed tomography between September 2015 and June 2017 at the Affiliated Hospital of Chengde Medical University, China. Logistic regression models were applied to analyze the risk factors for CCS ≥ 100 Agatston units (AU) and in different body mass index (BMI) subgroups.EAT and PAT volumes were noted to be higher in people with BMI ≥ 24 kg/m2, BMI ≥ 28 kg/m2, hyperlipidemia, hypertension, diabetes, stroke, and CCS ≥ 100 AU (P < 0.05). After adjusting for the traditional CAD factors, we found that EAT and PAT volumes were independent risk factors for CCS ≥ 100 AU (odds ratio, 3.001; 95% confidence interval, 1.900-4.740, P < 0.001). In patients with CCS ≥ 100 AU, the EAT and PAT volumes were noted to be greater in the BMI ≥ 24 kg/m2 and BMI ≥ 28 kg/m2 subgroups than in the BMI < 24 kg/m2 and BMI < 28 kg/m2 subgroups, respectively (P < 0.05).Our results indicate that EAT and PAT volumes may be clinical predictors for a CCS ≥ 100 AU, especially in overweight and obese individuals.

Abstract 14820: Pericardial Adipose Tissue Thrombospondin-1 Associates With Anti-Angiogenesis in Ischemic Heart Disease

Defective angiogenesis contributes to mechanisms of ischemic heart disease. Accumulation of ectopic pericardial adipose tissue has been associated with cardiovascular complications which, in part, may relate to adipose tissue-derived factors. We sought to characterize adipose tissue microvascular angiogenic capacity in individuals undergoing elective cardiac surgeries including aortic, valvular, and coronary artery bypass grafting (CABG). Pericardial fat was collected intraoperatively and examined for capillary sprouting capacity using an established ex vivo Matrigel-based methodology quantified for growth over seven days. Angiogenic capacity was significantly blunted (2.5-fold, p&lt;0.001) in subjects with CAD (age 59±2 years, BMI 32±1 kg/m 2 , LDL-C 92±45 mg/dl, n=37) compared to age-, BMI-, and LDL-cholesterol matched individuals without angiographic obstructive CAD (age 56±4 years, BMI 32±1 kg/m 2 , LDL-C 110±40 mg/dl, n=14). To garner potential mechanistic insight, we performed transcriptomic analyses using quantitative RT- PCR for select angiogenic regulators. We observed no significant differences in pericardial fat gene expression for pro-angiogenic mediators vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietin-1, or anti-angiogenic factors including soluble fms-like tyrosine kinase-1 (sFlt-1) and endostatin. In contrast, mRNA expression of anti-angiogenic thrombospondin-1 (TSP1) was significantly upregulated (2-fold, p&lt;0.05) in CAD subjects compared to the non-CAD group, which was confirmed by protein western-immunoblot analysis. Plasma concentrations of TSP-1 quantified by ELISA were not significantly different between the two groups. In summary, pericardial fat in subjects with CAD may be associated with an anti-angiogenic transcriptome linked to functional defects in vascularization capacity. Local paracrine actions of TSP1 in adipose depots surrounding the heart may play a role in mechanisms of ischemic heart disease.

Ectopic obesity in patients without manifested cardiovascular disease: regulations, frequency and clinical characteristics

To determine the frequency, distribution and characteristics of ectopic obesity in patients without manifested cardiovascular disease. We examined 320 patients without manifested cardiovascular disease (average age 63.813.9 years), 38 of them without cardiovascular risk factors (healthy referent group). Anthropometric indicators were measured, body mass index (BMI) was calculated. Degree, type of obesity, lipid profile were evaluated. All patients underwent multi-detector chest computed tomography in spiral mode on Toshiba Aquilion Prime scanner using standardized protocol. Perivascular adipose tissue (PVAT) and pericardial adipose tissue (PAT) were detected using specialized semi-automatic software Tissue Composition Module QCTPro (Mindways Software, Inc., USA) after scanner calibration with special phantom. PAT and PVAT exceeding the 90th percentile in the healthy referent group were considered as ectopic obesity. Statistical analysis was performed using Statistica 10.0 software (StatSoft Inc., USA). PAT volume 3.2 cm3 and PVAT volume 0.4 cm3 were criteria for high pericardial and high perivascular fat; 81 (25.2%) patients had ectopic obesity, 85 (26.5%) patients abdominal obesity; 146 (42.9%) people had high pericardial fat, 134 (39.4%) high perivascular fat. The frequency of ectopic obesity in patients with arterial hypertension (AH) was statistically significantly higher compared to persons without AH. Significantly more often ectopic forms of obesity were detected in patients with overweight and obesity. The high pericardial fat and high perivascular fat were found in patients with overweight and normal body weight. When comparing the clinical characteristics of patients with abdominal and ectopic obesity, metabolic parameters, as well as the incidence of hypertension and dyslipidemia, did not differ significantly. Ectopic obesity can develop outside of global obesity. In addition, this type of obesity is accompanied by metabolic disorders and AH, regardless of the abdominal distribution of adipose tissue.

Biomarkers extracted by fully automated body composition analysis from chest CT correlate with SARS-CoV-2 outcome severity

The complex process of manual biomarker extraction from body composition analysis (BCA) has far restricted the analysis of SARS-CoV-2 outcomes to small patient cohorts and a limited number of tissue types. We investigate the association of two BCA-based biomarkers with the development of severe SARS-CoV-2 infections for 918 patients (354 female, 564 male) regarding disease severity and mortality (186 deceased). Multiple tissues, such as muscle, bone, or adipose tissue are used and acquired with a deep-learning-based, fully-automated BCA from computed tomography images of the chest. The BCA features and markers were univariately analyzed with a Shapiro–Wilk and two-sided Mann–Whitney-U test. In a multivariate approach, obtained markers were adjusted by a defined set of laboratory parameters promoted by other studies. Subsequently, the relationship between the markers and two endpoints, namely severity and mortality, was investigated with regard to statistical significance. The univariate approach showed that the muscle volume was significant for female (pseverity ≤ 0.001, pmortality ≤ 0.0001) and male patients (pseverity = 0.018, pmortality ≤ 0.0001) regarding the severity and mortality endpoints. For male patients, the intra- and intermuscular adipose tissue (IMAT) (p ≤ 0.0001), epicardial adipose tissue (EAT) (p ≤ 0.001) and pericardial adipose tissue (PAT) (p ≤ 0.0001) were significant regarding the severity outcome. With the mortality outcome, muscle (p ≤ 0.0001), IMAT (p ≤ 0.001), EAT (p = 0.011) and PAT (p = 0.003) remained significant. For female patients, bone (p ≤ 0.001), IMAT (p = 0.032) and PAT (p = 0.047) were significant in univariate analyses regarding the severity and bone (p = 0.005) regarding the mortality. Furthermore, the defined sarcopenia marker (p ≤ 0.0001, for female and male) was significant for both endpoints. The cardiac marker was significant for severity (pfemale = 0.014, pmale ≤ 0.0001) and for mortality (pfemale ≤ 0.0001, pmale ≤ 0.0001) endpoint for both genders. The multivariate logistic regression showed that the sarcopenia marker was significant (pseverity = 0.006, pmortality = 0.002) for both endpoints (ORseverity = 0.42, 95% CIseverity: 0.23–0.78, ORmortality = 0.34, 95% CImortality: 0.17–0.67). The cardiac marker showed significance (p = 0.018) only for the severity endpoint (OR = 1.42, 95% CI 1.06–1.90). The association between BCA-based sarcopenia and cardiac biomarkers and disease severity and mortality suggests that these biomarkers can contribute to the risk stratification of SARS-CoV-2 patients. Patients with a higher cardiac marker and a lower sarcopenia marker are at risk for a severe course or death. Whether those biomarkers hold similar importance for other pneumonia-related diseases requires further investigation.

Central role of PD-L1 in cardioprotection resulting from P2Y4 nucleotide receptor loss.

A better understanding of the immune function of pericardial adipose tissue is essential to adapt treatments after myocardial infarction. We showed previously that inactivation of mouse P2Y4 nucleotide receptor induces adiponectin overexpression and protection against myocardial infarction. We investigated here the inflammatory state of pericardial adipose tissue in ischemic P2Y4-deficient mice. We demonstrated that P2Y4-deficient mice displayed adipocyte beiging with increased PD-L1 expression and a higher number of regulatory leukocytes in their pericardial adipose tissue after left anterior descending artery ligation, compared to wild type mice. Effectively, a higher level of anti-inflammatory M2c macrophages and regulatory T cells was observed in pericardial adipose tissue of P2Y4 KO mice and correlated with reduced post-ischemic expansion of fat-associated lymphoid clusters. Interestingly, the anti-inflammatory effects observed in P2Y4 KO mice, were no more observed in P2Y4/adiponectin double KO ischemic mice. Finally, the reduction of T cell infiltration and cardiac fibrosis observed in P2Y4-deficient heart was lost after injection of anti-PD-L1 blocking antibody in ischemic mice. The present study defines P2Y4 as a regulator of PD-L1 and adiponectin, and as a potential target for anti-inflammatory therapies to improve myocardial infarction outcome. The combined effect of P2Y4 loss on adipocyte beiging and regulatory leukocyte increase highlights this nucleotide receptor as an important player in post-ischemic cardiac response.

The Importance of the Assessment of Epicardial Adipose Tissue in Scientific Research.

Epicardial adipose tissue (EAT) exhibits morphological similarities with pericardial adipose tissue, however, it has different embryological origin and vascularization. EAT is a metabolically active organ and a major source of anti-inflammatory and proinflammatory adipokines, which have a significant impact on cardiac function and morphology. Moreover, it can regulate vascular tone by releasing various molecules. The relationship between EAT and cardiovascular disease and diseases of other organ systems is now considered a common discussion subject. The present clinical review article summarizes the epidemiological findings based on imaging techniques in studies conducted so far. In conclusion, evaluation of the epicardial adipose tissue constitutes a helpful scientific parameter, which can be assessed by means of different diagnostic imaging examinations.

Relationship of coronary calcinosis and local fat deposts in patients with coronary artery disease

Highlights. Taking into account the connection between the increase in the volume of myocardial adipose tissue and vessels with massive calcification of the coronary arteries in coronary heart disease, morphometry of epicardial and perivascular adipose tissue during routine tomographic examinations can be considered as a non-invasive technique for determining a surrogate marker of severe coronary lesion.Aim. To evaluate the relationship of coronary artery calcification (CA) and morphometric parameters of local fat depots in patients with coronary heart disease (CHD).Methods. 125 patients with stable coronary artery disease aged 59±8.9 years were examined. Visualization of local fat depots, abdominal fat depots, and coronary calcification (CC) was performed using multislice computed tomography with subsequent post-processing of images on the Siemens Leonardo workstation (Germany). Non-contrast magnetic resonance imaging of the heart was used to determine the EAT thickness.Results. Coronary calcification was detected in 95.2% of the examined patients with coronary artery disease (n = 119). There were higher indices of the EAT thickness of the right and left ventricles in case of massive CC, the thickness of the pericardial adipose tissue at the level of the trunk of the left coronary, anterior descending, circumflex arteries, and increased morphometry indices of the abdominal fat depot in comparison with the patients who had moderate and medium CC.Conclusion. An increase in the volume of adipose tissue of the myocardium and vessels in CAD is associated with massive calcification, which is reflected in the pathogenetic “adipovascular” continuum, characterized by the stimulation of adipogenesis against the background of atherocalcinosis of the coronary arteries. Morphometry of epicardial and perivascular adipose tissue during routine tomographic studies is a non-invasive technique for determining a surrogate marker of severe coronary lesions.

Exosomes derived from pericardial adipose tissues attenuate cardiac remodeling following myocardial infarction by Adipsin-regulated iron homeostasis.

As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury. In vitro experiments were conducted to evaluate the effects of Adipsin on cardiomyocyte function in the face of hypoxic challenge and the mechanisms involved. Our results showed that Adipsin dramatically altered expression of proteins associated with iron metabolism and ferroptosis. In vivo results demonstrated that Adipsin upregulated levels of Ferritin Heavy Chain (FTH) while downregulating that of Transferrin Receptor (TFRC) in peri-infarct regions 1 month following MI. Adipsin also relieved post-MI-associated lipid oxidative stress as evidenced by decreased expression of COX2 and increased GPX4 level. Co-immunoprecipitation and immunofluorescence imaging prove a direct interaction between Adipsin and IRP2. As expected, cardioprotection provided by Adipsin depends on the key molecule of IRP2. These findings revealed that Adipsin could be efficiently delivered to the heart by exosomes derived from pericardial adipose tissues. In addition, Adipsin interacted with IRP2 to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. Therefore, Adipsin-overexpressed exosomes derived from pericardial adipose tissues may be a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury.

The association of pericardial fat and peri-aortic fat with severity of nonalcoholic fatty liver disease

Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P < 0.001) and TAT (11.2 ± 4.1 vs. 7.6 ± 2.6 vs. 5.5 ± 2.6 ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82–0.89 and 0.84–0.90). Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

Ten-Year Changes in Television Viewing and Physical Activity Are Associated With Concurrent 10-Year Change in Pericardial Adiposity: The Coronary Artery Risk Development in Young Adults Study.

Longitudinal association of television (TV) viewing and moderate- to vigorous-intensity physical activity (MVPA) with pericardial adipose tissue (PAT) is unclear. We studied Coronary Artery Risk Development in Young Adults Study participants transitioning from early to middle age at Coronary Artery Risk Development in Young Adults (CARDIA) exam years 15 (2000-2001; N = 1975, mean age = 40.4, 55.4% women, 45.3% Black) and 25 (2010-2011). TV viewing (in hours per day) and MVPA (in exercise units) were measured using a self-report questionnaire. PAT volume (in milliliters) was measured using computed tomography. Multivariable linear regression was used to examine the associations of tertiles of 10-year change (years 25-15) in TV viewing and MVPA with a concurrent change in PAT with adjustments for covariates. Participants in the highest tertile of 10-year increase in TV viewing had a greater increase in PAT (β = 2.96mL, P < .01). Participants in both middle (β = -3.93mL, P < .01) and highest (β = -6.22mL, P < .01) tertiles of 10-year changes in MVPA had smaller mean increases in PAT over 10years when compared with the lowest tertile in fully adjusted models. Reducing or maintaining early-midlife levels of TV viewing and increasing MVPA may be associated with less PAT accumulation with age.

Relationship of Subcutaneous Adipose Tissue Inflammation-Related Gene Expression With Ectopic Lipid Deposition in Persons With HIV.

Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART. A total of 92 PWH with well-controlled viremia underwent computed tomography imaging and abdominal SAT biopsy for gene expression analysis. SAT gene expression was measured using a NanoString panel of 255 immune-related genes. Associations between gene expression and computed tomography measurements of the volume and attenuation (radiodensity) of metabolically relevant ectopic fat depots were assessed using multivariable linear regression and network analysis. Greater SAT volume was associated with higher visceral and pericardial adipose tissue volume, but lower skeletal muscle attenuation. Lower SAT attenuation, a measure of lipid content, was associated with lower visceral adipose tissue attenuation. Hierarchical clustering identified a subset of macrophage-related genes in SAT, including CCL2, CCL22, CCL13, CCR1, CD86, CD163, IL-6, IL-10, MRC1, and TREM2, which were associated with an increased lipid deposition in multiple ectopic depots. Altered expression of macrophage-related genes in SAT is associated with differences in ectopic fat depot morphometrics among PWH on long-term ART, including in the pericardial and visceral compartments. These findings provide basis for future studies to assess host, virus, and treatment factors shaping the SAT immune environment and its effects on morphometric changes and metabolic comorbidities in PWH.

Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.

AimsWe evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying mechanism in 42 598 UK Biobank participants.Methods and resultsWe extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships.ConclusionWe demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk.

Recent Progress in Epicardial and Pericardial Adipose Tissue Segmentation and Quantification Based on Deep Learning: A Systematic Review

Epicardial and pericardial adipose tissues (EAT and PAT), which are located around the heart, have been linked to coronary atherosclerosis, cardiomyopathy, coronary artery disease, and other cardiovascular diseases. Additionally, the volume and thickness of EAT are good predictors of CVD risk levels. Manual quantification of these tissues is a tedious and error-prone process. This paper presents a comprehensive and critical overview of research on the epicardial and pericardial adipose tissue segmentation and quantification methods, evaluates their effectiveness in terms of segmentation time and accuracy, provides a critical comparison of the methods, and presents ongoing and future challenges in the field. Described methods are classified into pericardial adipose tissue segmentation, direct epicardial adipose tissue segmentation, and epicardial adipose tissue segmentation via pericardium delineation. A comprehensive categorization of the underlying methods is conducted with insights into their evolution from traditional image processing methods to recent deep learning-based methods. The paper also provides an overview of the research on the clinical significance of epicardial and pericardial adipose tissues as well as the terminology and definitions used in the medical literature.

Differential remodelling of visceral and pericardial adipose tissue in response to stress and exercise

Obesity is driven by an imbalance between caloric intake and energy expenditure, causing excessive storage of nutrients in adipose tissue at different sites around the body. Increased visceral adipose tissue (VAT) is associated with diabetes, whilst pericardial adipose tissue (PAT) is associated with cardiac pathology. Adipose tissue can expand either through cellular hypertrophy or hyperplasia, with the former correlating with decreased metabolic health in obesity. The aim of this study was to determine how VAT and PAT remodel in response to obesity, stress and exercise.Here we have used the obese Zucker rats which develop hyperphagia with reduced energy expenditure, resulting in morbid obesity as a result of leptin resistance. At 9 weeks of age lean (LZR) and obese (OZR) Zucker male rats were treated with or without unpredictable chronic mild stress or exercise for 8 weeks. To determine the phenotype for PAT and VAT, tissue cellularity and gene expression were analyzed. Tissue cellularity was determined following haematoxylin and eosin staining, whilst qPCR was used to examine gene expression.PAT adipocytes were significantly smaller than those from VAT and had a more biege‐like appearance. In the OZR group, VAT adipocyte cell size increased significantly compared with LZR, whilst PAT showed no change. Exercise and stress resulted in a significant reduction in VAT cellularity in OZR, whilst PAT showed no change. This suggests that PAT cellularity does not remodel significantly compared with VAT. Picro sirus red staining indicated that PAT had significantly more fibrosis than VAT. However, this fibrosis was decreased following stress treatment. This data indicate that the extracellular matrix of PAT is able to remodel more readily than in VAT.Gene expression analysis showed that PAT expressed higher levels of UCP1 compared with VAT, indicating that it has a more brown‐like phenotype. In the LZR group, exercise increased insulin receptor substrate 1 (IRS1) in PAT, but was decreased in the OZR group. On the other hand, in VAT, exercise decreased IRS1 in LZR, whilst increasing it in the OZR. This suggests that in obesity, VAT is more responsive to exercise and subsequently becomes less insulin resistant compared with PAT. In VAT, stress increased PPAR‐γ expression in the OZR group but decreased it in the PAT. This suggests that in obesity, stress increases adipogenesis more significantly in the VAT compared with PAT.Taken together, our data suggest that VAT is considerably more plastic than PAT and remodels rapidly in response to obesity, exercise and psychological stress.

Adipose Tissue Compartments, Inflammation, and Cardiovascular Risk in the Context of Depression.

The neurobiological and behavioral underpinnings linking mental disorders, in particular, major depressive disorder (MDD), with cardiovascular disorders are a matter of debate. Recent research focuses on visceral (intra-abdominal and epicardial) adipose tissue and inflammation and their impact on the development of cardiometabolic disorders. Intra-abdominal adipose tissue is defined as an endocrine active fat compartment surrounding inner organs and is associated with type 2 diabetes mellitus, a risk factor for the later development of cardiovascular disorders. Epicardial (pericardial) adipose tissue is a fat compartment surrounding the heart with close proximity to the arteries supporting the heart. Visceral adipose tissue (VAT) is an important source of inflammatory mediators that, in concert with other risk factors, plays a leading role in cardiovascular diseases. In conjunction with the behavioral (physical inactivity, sedentary lifestyle), psychological (adherence problems), and hormonal (dysfunction of the hypothalamus–pituitary–adrenal axis with subsequent hypercortisolism) alterations frequently accompanying MDD, an enhanced risk for cardiovascular disorders results.

Longitudinal pericardial adipose tissue changes in patients with breast cancer receiving anthracycline-based chemotherapy: a retrospective cohort study.

Pericardial adipose tissue (PAT) has been associated with adverse cardiac events. In this study, we evaluated changes of PAT in patients with breast cancer during and after anthracycline-based chemotherapy and explored the clinical variables associated with increases in PAT volume at the completion of chemotherapy. A total of 278 breast cancer patients who were receiving anthracycline-based chemotherapy were retrospectively enrolled. Their PAT volumes were measured using non-contrast chest computed tomography (CT) images from a dedicated workstation. We compared these volumes to their measurements at baseline, during different chemotherapy cycles, at and after chemotherapy completion. We identified the clinical variables associated with increases in PAT volume at chemotherapy completion using logistic regression analyses. At the completion of chemotherapy, PAT volumes were shown to have increased compared to baseline measurements (87.67±45.09 vs. 104.25±47.74 cm3; P=0.00). After 4, 6, and 8 chemotherapy cycles, PAT volumes increased from the baseline measurement by 9.48% [95% confidence interval (CI): -2.30% to 21.27%], 14.75% (95% CI: 4.68% to 24.82%), and 20.02% (95% CI: 11.38% to 28.66%), respectively. Compared to volumes measured at chemotherapy completion (104.25±47.74 cm3), PAT volumes at 6 and 12 months after chemotherapy completion were 105.23±49.27 and 107.56±46.34 cm3, respectively. The differences between chemotherapy completion and follow-up PAT volumes were not statistically significant. A variable associated with an increase in PAT from baseline to chemotherapy completion was the number of chemotherapy cycles (8 vs. 4) [odds ratio (OR) =3.850; 95% CI: 1.751 to 8.488]. Patients with breast cancer who undergo anthracycline-based chemotherapy can experience unfavorable PAT volume increases, which are maintained after the completion of treatment. Patients at risk of increases in PAT volume at chemotherapy completion can be identified based on clinical risk factors and targeted for interventions.

The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery

Background and aimsEpicardial and pericardial adipose tissue (EAT and PAT) associate with atherosclerosis, however, discussed to have different inflammatory properties. We examined the NLRP3 inflammasome related pathway, playing a pivotal role in atherosclerosis, in EAT, PAT and subcutaneous AT (SAT), their relationship to cell types and anthropometric measures in patients undergoing coronary artery bypass grafting. MethodsBiopsies from EAT, PAT and SAT were collected from 52 patients with coronary heart disease (CHD) (median body weight 85.0 kg) and 22 controls. RNA was extracted and expression of interleukin (IL)-1β, IL-18, NLRP3, Caspase-1, toll-like receptor 4 (TLR4), IL-6, IL-6 receptor and gp130 were analyzed by RT-PCR. ResultsLimited differences in any genes between CHD patients and controls. IL-18 and IL-6 were 4-fold higher expressed in EAT versus PAT (p < 0.01, both) and SAT (p < 0.001, both), whereas caspase-1, IL-6R and gp130 were higher expressed in SAT compared to the other compartments (all p = 0.06-<0.001). Significant correlations between SAT and PAT gene expressions (r = 0.358–0.579, all p ≤ 0.01). Especially NLRP3 and TLR4 associated with the expression of macrophages in all compartments (all p < 0.001). In EAT IL-18 correlated inversely with the expression of macrophages and T-cells. In SAT and PAT most of the mediators associated with body weight. ConclusionsHigher expression of IL-18 and IL-6 was observed in EAT in our non-obese CHD patients, not related to inflammatory cells. The NLRP3 inflammasome activation in SAT that mirrored PAT, both related to anthropometrics, suggest that SAT samples, being easily available, to a certain degree, represent adipose tissue inflammation in general.

Cardiorespiratory Fitness in Adults Aged 18 to 34 Years and Long-Term Pericardial Adipose Tissue (from the Coronary Artery Risk Development in Young Adults Study)

Pericardial adipose tissue (PAT), an ectopic adipose depot surrounding the coronary arteries, is a pathogenic risk marker for cardiometabolic disease; however, the association between cardiorespiratory fitness (CRF) and PAT is unclear. Young adults (n=2,614, mean age 25.1 years, 55.8% women, and 43.8% Black at baseline [1985 to 1986]) from the Coronary Artery Risk Development in Young Adults study were included. Maximal CRF was estimated at baseline, examination year 7 (1992 to 1993) and year 20 (2005 to 2006), using a symptom-limited maximal treadmill exercise test (duration in minutes) among those achieving ≥85% of age-predicted maximal heart rate. PAT volume (ml) was quantified at examination year 15 (2000 to 2001) and year 25 (2010 to 2011) using computed tomography. Multivariable linear and linear mixed regressions with covariates (sociodemographics, cardiovascular disease risk factors, inflammation, waist circumference) from baseline, year 7, and/or year 20 were used. Separate multivariable regression models revealed inverse associations of CRF at baseline, year 7, or year 20 with PAT at year 25 in fully adjusted models (all p <0.001). The linear mixed model showed that a 1-minute increase in treadmill exercise test duration over 20 years was associated with 1.49 ml lower subsequent PAT volume (p <0.001). In conclusion, findings suggest that higher CRF is inversely associated with subsequent PAT volume. Strategies to optimize CRF may be preventive against excessive PAT accumulation with age.

Epicardial and pericardial fat analysis on CT images and artificial intelligence: a literature review.

The present review summarizes the available evidence on artificial intelligence (AI) algorithms aimed to the segmentation of epicardial and pericardial adipose tissues on computed tomography (CT) images. Body composition imaging is a novel concept based on quantitative analysis of body tissues. Manual segmentation of medical images allows to obtain quantitative and qualitative data on several tissues including epicardial and pericardial fat. However, since manual segmentation requires a considerable amount of time, the analysis of adipose tissue compartments based on AI has been proposed as an automatic, reliable, accurate and fast tool. The literature research was performed on March 2021 using MEDLINE PubMed Central and "adipose tissue artificial intelligence", "adipose tissue deep learning" or "adipose tissue machine learning" as keywords for articles search. Relevant articles concerning epicardial adipose tissue, pericardial adipose tissue and AI were selected. The evaluation of adipose tissue compartments can provide additional information on the pathogenesis and prognosis of several diseases, including cardiovascular. AI can assist physicians to obtain important information, possibly improving the patient's quality of life and identifying patients at risk of developing variable disorders.