Most forms of obesity are associated with chronic diseases that remain a global public health challenge.

Despite significant advancements in understanding its pathophysiology, effective management of obesity is hindered by the persistence of knowledge gaps in epidemiology, phenotypic heterogeneity and policy implementation.

This consensus statement by the European Society for Clinical Investigation identifies eight critical areas requiring urgent attention. Key gaps include insufficient long-term data on obesity trends, the inadequacy of body mass index (BMI) as a sole diagnostic measure, and insufficient recognition of phenotypic diversity in obesity-related cardiometabolic risks. Moreover, the socio-economic drivers of obesity and its transition across phenotypes remain poorly understood.

The syndemic nature of obesity, exacerbated by globalization and environmental changes, necessitates a holistic approach integrating global frameworks and community-level interventions. This statement advocates for leveraging emerging technologies, such as artificial intelligence, to refine predictive models and address phenotypic variability. It underscores the importance of collaborative efforts among scientists, policymakers, and stakeholders to create tailored interventions and enduring policies.

The consensus highlights the need for harmonizing anthropometric and biochemical markers, fostering inclusive public health narratives and combating stigma associated with obesity. By addressing these gaps, this initiative aims to advance research, improve prevention strategies and optimize care delivery for people living with obesity.

This collaborative effort marks a decisive step towards mitigating the obesity epidemic and its profound impact on global health systems. Ultimately, obesity should be considered as being largely the consequence of a socio-economic model not compatible with optimal human health.

Asthma and cardiovascular diseases (CVDs) are the 2 common and complex health problems with a substantial global impact. Epidemiological studies indicate that asthma and CVDs are common, with evidence supporting their cooccurrence. Inflammation, oxidative stress, obesity, metabolic syndrome, smoking, secondhand smoke exposure, physical inactivity, and environmental exposures are all risk factors for asthma and CVDs. In addition, inflammatory and immunological pathways, autonomic dysfunction, endothelial dysfunction, thrombosis, coagulation, and common genetic risk factors contribute to the asthma-CVD relationship. Asthmatic individuals have higher morbidity and mortality rates related to CVDs and high-risk factors. Techniques such as screening for CVDs in asthma patients, pharmaceutical therapy, and lifestyle changes are critical for effectively managing these comorbid illnesses. Understanding the link between asthma and CVD is necessary for integrated and clinical management approaches to enhance patient outcomes and lessen the burden of these related diseases.

Diabetic cardiomyopathy is a unique cardiomyopathy that is common in diabetic patients, and it is also a diabetic complication for which no effective treatment is currently available. Moreover, relevant studies have revealed that a link exists between type 2 diabetes and heart failure and that abnormal thickening of EAT is inextricably linked to the development of diabetic heart failure. Numerous clinical studies have demonstrated that EAT is implicated in the pathophysiologic process of diabetic myocardial disease. In this overview, we will introduce the physiology, pathophysiology of the disease and potential therapeutic strategies, knowledge gaps, and future directions of the role of epicardial adipose tissue in type 2 diabetes mellitus and heart failure to promote the development of novel therapeutic approaches to improve the prognosis of patients with diabetic cardiomyopathy.

The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardiorenal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardiometabolic pathologies.

Excessive accumulation of epicardial adipose tissue (EAT) is known to be a risk factor for coronary artery disease and heart failure. In particular, it is thought that inflammation of pericoronary adipose tissue (PCAT) affects the pathology of various coronary artery diseases (CAD). EAT and PCAT are thought to be new therapeutic targets for preventing cardiovascular disease. Although there are no established drugs that specifically reduce inflammation of EAT or PCAT, the basic approach is to improve lifestyle-related diseases through exercise and diet, and to use metabolic improvement drugs and anti-inflammatory drugs as soft support. Potential candidates include statins, SGLT2 inhibitors, and GLP- 1 receptor agonists. In addition to conventional treatments that target substances within blood vessels, treatments that target EAT and PCAT by directly enveloping the coronary arteries and myocardium from outside the body are expected to further suppress cardiovascular events.

Anthracyclines are widely used in cancer treatment, yet their potential for anthracycline-induced cardiotoxicity (AIC) limits their clinical utility. Despite the significant anatomical relevance of pericardial adipose tissue (PeAT) to cardiovascular disease, its response to anthracycline exposure remains poorly understood.

Male New Zealand White rabbits (n=17) received weekly doxorubicin injections and underwent magnetic resonance imaging (MRI) scans biweekly for 10 weeks. PeAT volumes (total, left paraventricular, right paraventricular) were measured together with ventricular function. Histopathological evaluations were also conducted. A mixed linear model identified the earliest timeframe for detectable changes in PeAT volume and left ventricular function. Total PeAT volume decreased from the 6th week (1.17±0.06, P<0.05) and continued to decrease until the 8th week (0.96±0.06, P<0.05) and left paraventricular adipose tissue volume decreased significantly, but no changes were observed in right paraventricular adipose tissue volume. The volume of PeAT exhibited a positive correlation with left ventricular ejection fraction (LVEF) (r=0.43, P<0.05), which declined below 50% by the 8th week, and a negative correlation with myocardial cell injury scores (r=-0.595, P<0.05).

Anthracycline administration led to an early reduction in PeAT volume, particularly in the left paraventricular region, detectable by MRI as early as the 6th week. Changes in PeAT volume preceded alterations in LVEF and were associated with declines in cardiac function and myocardial cell damage.

We hypothesize that epicardial adipose tissue (EAT) structure differs between patients with coronary disease and healthy individuals and that EAT may undergo changes during an acute coronary syndrome (ACS). This study aimed to investigate EAT thickness (EATt) and structure using ultrasound radiomics in patients with ACS, patients with chronic coronary syndrome (CCS), and controls and compare the findings between the three groups. This prospective monocentric comparative cohort study included three patient groups: ACS, CCS, and asymptomatic controls. EATt was assessed using transthoracic echocardiography. Geometrical features (as mean gray value and raw integrated density) and texture features (as angular second moment, contrast and correlation) were computed from grayscale Tagged Image File Format biplane images using ImageJ software. EATt did not significantly differ between the ACS group (8.14 ± 3.17 mm) and the control group (6.92 ± 2.50 mm), whereas CCS patients (9.96 ± 3.19 mm) had significantly thicker EAT compared to both the ACS group (p = 0.025) and the control group (p < 0.001). Radiomics analysis revealed differences in geometrical parameters with discriminatory capabilities between both ACS group and controls and CCS group and controls. A multivariate analysis comparing ACS and CCS patients revealed that differences in EAT characteristics were significant only in patients with a body mass index below 26.25 kg/m². In this subgroup, patients older than 68 exhibited a higher modal gray value (p = 0.016), whereas those younger than 68 had a lower minimum gray value (p = 0.05). Radiomic analysis highlights its potential in developing imaging biomarkers for early diagnosis and coronary artery disease progression monitoring.

Epicardial fat density (EFD) is implicated in cardiovascular diseases. This study aimed to assess the regional variability of epicardial fat density (EFD) using coronary computed tomography (CCT) and evaluate the feasibility of ROI-based measurements as an alternative to full segmentation. A retrospective analysis was conducted on 171 patients undergoing coronary CCT. EFD was measured on non-contrast scans acquired globally and in three predefined regions of interest (ROIs) for coronary calcium scoring: the aortic bulb, right posterolateral wall, and cardiac apex. Global EFD was quantified using semi-automated segmentation software (3D Slicer 5.6.2), while regional EFD values were manually determined. Statistical analyses were performed to compare global and regional EFD measurements. Global EFD averaged -83.92 ± 5.19 HU, while regional EFD showed significant variability. The aortic bulb had lower EFD values (-97.54 ± 12.80 HU) compared to the apex (-93.42 ± 18.94 HU) and right posterolateral wall (-94.99 ± 12.16 HU). Paired t-tests confirmed statistically significant differences between global and regional EFD values (p < 0.000). This study highlights significant regional variability in EFD across specific cardiac regions, suggesting that ROI-based assessments may not reliably reflect global EFD characteristics.

In the United States, two out of every five adults have obesity. The obesity epidemic is a significant public health concern and a major risk factor for atherosclerotic cardiovascular disease (ASCVD), contributing to its development through a complex interplay of social, biologic and behavioral mechanisms. It exacerbates traditional cardiovascular risk factors such as dyslipidemia, hypertension, and type 2 diabetes, while visceral and epicardial fat deposition promotes inflammation and insulin resistance, thereby accelerating atherosclerosis. Beyond traditional pathophysiologic pathways, social determinants of health (SDoH) significantly contribute to obesity-related disparities, particularly among racial and ethnic minorities. SDoH factors such as socioeconomic status, access to health care, and limited availability of nutritious food and safe spaces for physical activity not only increase obesity prevalence but also exacerbate its psychological toll, including stress and anxiety, which further elevate cardiovascular risk. Environmental factors, such as limited green spaces and air pollution, further promote obesogenic behaviors and worsen cardiovascular outcomes. In this review, we explore the association between obesity and ASCVD and key mediating pathways including the role of SDoH and environmental risk factors. We also discuss potential strategies-including patient education, community engagement to address SDoH, and establishment of dedicated cardiometabolic and cardiovascular prevention clinics-to mitigate the population burden of obesity and improve downstream cardiovascular outcomes.

The relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. The purpose of this study was to investigate the role of KCa3.1 in the migration of macrophages from EAT to adjacent atrial tissue during rapid pacing.

Part 1: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + clodronate liposome (CL) group. Part 2: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + TRAM-34 group. HL-1 cells and RAW264.7 cells were co-cultured to explore the specific migratory mechanism of macrophages.

Depleting EAT macrophages significantly reduced macrophage infiltration in the adjacent atrium and the induction of AF in canines with rapid atrial pacing. TRAM-34 significantly inhibited the migration of macrophages from EAT to the adjacent atrium and electrical remodelling in canines with rapid atrial pacing. Compared with those of the control HL-1 cells, the secretion of CCL2 and the number of migrating macrophages in pacing HL-1 cells was significantly increased, which could be reversed by TRAM-34. Further in vitro experiments showed that KCa3.1 regulated CCL2 secretion through the p65/STAT3 signalling pathway.

Inhibiting myocardial KCa3.1 reduced the migration of EAT macrophages to adjacent atrial muscles caused by rapid atrial pacing, thereby decreasing vulnerability to AF. The mechanism by which KCa3.1 regulates CCL2 may be related to the p65/STAT3 signalling pathway.

Lifestyle-related diseases, such as atherosclerosis and diabetes, are now considered to be a series of diseases caused by chronic inflammation. Adipose tissue is considered to be an endocrine organ that not only plays a role in lipid storage, heat production, and buffering, but also produces physiologically active substances and is involved in chronic inflammation. Perivascular adipose tissue (PVAT) surrounding blood vessels similarly produces inflammatory and anti-inflammatory physiologically active substances that act on blood vessels either directly or via the bloodstream. Epicardial adipose tissue (EAT), which is in direct contact with the coronary arteries inside the pericardium, is thought to have a direct effect on the coronary arteries as well. The presence and inflammatory status of these adipose tissues can be evaluated by imaging tests, and has been shown to be associated with the presence of current cardiovascular disease (CVD) and to be a prognostic factor. It is also expected to become a new diagnostic and therapeutic target for CVD.

Epicardial adipose tissue (EAT) is a fat depot covering the heart. No physical barrier separates EAT from the myocardium, so EAT can easily affect the underlying cardiac muscle. EAT can participate in the development and progression of heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). In healthy humans, excess EAT is associated with impaired cardiac function and worse outcomes. In HFpEF, this trend continues: EAT amount is usually increased, and excess EAT correlates with worse function/outcomes. However, in HFrEF, the opposite is true: reduced EAT amount correlates with worse cardiac function/outcomes. Surprisingly, although EAT has beneficial effects on cardiac function, it aggravates ventricular arrhythmias. Here, we dissect these phenomena, trying to explain these paradoxical findings to find a target for novel heart failure therapies aimed at EAT rather than the myocardium itself. However, the success of this approach depends on a thorough understanding of interactions between EAT and the myocardium.

Huangqi-Danshen decoction (HDD) is a classic traditional Chinese medicine for treating heart failure. Pericardial adipose tissue (PAT) has recently gained increasing attention in cardiovascular diseases.

This study aimed to investigate the effect of pericardial adipose tissue-derived extracellular vesicles on heart failure, the protective effect of HDD on myocardial remodel in heart failure rats, and identify the potential molecular mechanisms involved.

UPLC-MS/MS identified active components of HDD. Extracellular vesicles (EVs) from pericardial adipose tissue of sham-operated and HF rats were identified through transmission electron microscopy, nanoparticle tracking analysis and western blot. EVs were co-cultured with H9c2 cardiomyocytes in order to examine their uptake and effects. MicroRNA sequencing, dual-luciferase reporter assay and PCR were conducted for exploring specific mechanisms of EVs on hypertrophic cardiomyocytes. In vivo, heart failure was modeled in rats via transverse aortic constriction (TAC). In vitro, the hypertrophic cardiomyocyte model were established using Ang II-induced H9c2 cardiomyocytes.

UPLC-MS/MS identified 11 active components in serum of HDD administrated rats. Echocardiography showed HDD improved cardiac function in TAC model rats. HE and Masson staining indicated HDD ameliorated myocardial hypertrophy and fibrosis. MicroRNA sequencing found that HDD treatment resulted in 37 differentially expressed miRNAs (DMEs) (p < 0.05 and |log2FC| ≥ 1). KEGG analysis revealed that DEMs were enriched in the AMPK signaling pathway. PCR identified miR-27a-3p with the greatest difference in AMPK-related DMEs. Dual-luciferase reporter assay and Targetscan website were utilized to identify the target relationship between miR-27a-3p and PRKAA2 (AMPKα2). The miR-27a-3p negatively regulated AMPKα2 to inhibit mitophagy mediated by PINK1/Parkin pathway. HDD inhibited miR-27a-3p secretion from failing heart pericardial adipose tissue-derived extracellular vesicles, thereby improving inflammation, cardiac function, and myocardial remodeling through above pathways.

HDD inhibited the PAT-derived extracellular vesicular miR-27a-3p in failing hearts to activate AMPK/PINK1/Parkin signaling-mediated mitophagy, which improved cardiomyocyte energy metabolism, myocardial remodeling and heart failure.

Epicardial adipose tissue (EAT) deposition has been long associated with heart weight. However, recent research has failed to replicate this association. We aimed to determine the association of EAT volume with heart weight in post-mortem cases and identify potential confounding variables. EAT volume derived from post-mortem computed tomography (PMCT) and heart weight were measured in post-mortem cases (N = 87, age: 56 ± 16 years, 28% female). Cases with hypertrophied heart weights (N = 44) were determined from reference tables. Univariable associations were tested using Spearman correlation and simple linear regression. Independence was determined with stepwise regression. In the total cohort, EAT volume (median 66 ± 45 cm3) was positively associated with heart weight (median 435 ± 132 g) at the univariable level (r = 0.6, P < 0.0001) and after adjustment for age, female sex, and various body size metrics (R2 adjusted = 0.41-0.57). Median EAT volume was 1.9-fold greater in cases with hypertrophic hearts (P < 0.0001) but with considerably greater variability, especially in cases with extreme EAT volume or heart weight. As such, EAT volume was not associated with heart weight in hypertrophic cases, while a robust independent association was found in non-hypertrophic cases (R2 adjusted = 0.62-0.86). EAT mass estimated from EAT volume found that EAT comprised approximately 13% of overall heart mass in the total cases. This was significantly greater in cases with hypertrophy (median 15.5%; range, 3.6-36.6%) relative to non-hypertrophied cases (12.5%, 3.3-24.3%) (P = 0.04). EAT volume is independently and positively associated with heart weight in post-mortem cases. Excessive heart weight significantly confounded this association.

In the last forty years, the number of people over 60 years of age has increased significantly owing to better nutrition and lower rates of infectious diseases in developing countries. Aging significantly impacts adipose tissue, which plays crucial role in hormone regulation and energy storage. This can lead to imbalances in glucose, and overall energy homeostasis within the body. Aging is irreversible phenomena and potentially causing lipid infiltration in other organs, leading to systemic inflammation, metabolic disorders. This review investigates various pathways contributing to aging-related defects in adipogenesis, such as changes in adipose tissue function and distribution. Polyphenols, a diverse group of natural compounds, can mitigate aging effects via free radicals, oxidative stress, inflammation, senescence, and age-related diseases. Polyphenols like resveratrol, quercetin and EGCG exhibit distinct mechanisms and regulate crucial pathways, such as the TGF-β, AMPK, Wnt, PPAR-γ, and C/EBP transcription factors, and influence epigenetic modifications, such as DNA methylation and histone modification. This review highlights the critical importance of understanding the intricate relationship between aging and adipogenesis for optimizing well-being with increasing age. These findings highlight the therapeutic potential of polyphenols like quercetin and resveratrol in enhancing adipose tissue function and promoting healthy aging.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as pivotal medications for heart failure, demonstrating remarkable cardiovascular benefits extending beyond their glucose-lowering effects. The unexpected cardiovascular advantages have intrigued and prompted the scientific community to delve into the mechanistic underpinnings of these novel actions. Preclinical studies have generated many mechanistic theories, ranging from their renal and extrarenal effects to potential direct actions on cardiac muscle cells, to elucidate the mechanisms linking these drugs to clinical cardiovascular outcomes. Despite the strengths and limitations of each theory, many await validation in human studies. Furthermore, whether SGLT2 inhibitors confer therapeutic benefits in specific subsets of cardiomyopathies akin to their efficacy in other heart failure populations remains unclear. By examining the shared pathological features between heart failure resulting from vascular diseases and other causes of cardiomyopathy, certain specific molecular actions of SGLT2 inhibitors (particularly those targeting cardiomyocytes) would support the concept that these medications will yield therapeutic benefits across a broad range of cardiomyopathies. This article aims to discuss the important mechanisms of SGLT2 inhibitors and their implications in hypertrophic and dilated cardiomyopathies. Furthermore, we offer insights into future research directions for SGLT2 inhibitor studies, which hold the potential to further elucidate the proposed biological mechanisms in greater detail.

This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery. EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, p = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol H2O2/g tisssue/h vs. 15.7 ± 1.55 nmol H2O2/g tisssue/h, p < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery.

Epicardial adipose tissue (EAT) is a unique fat depot located between the myocardium and the visceral layer of pericardium. It can be further subdivided into pericoronary (PCAT), periatrial (PAAT) and periventricular adipose tissue (PVentAT), each of them exhibiting specific characteristics and association with the underlying tissue. Since no physical barrier separates EAT from the myocardium, this fat tissue can easily interact with the underlying cardiac structure. EAT can be visualized using various imaging modalities. Computed tomography provides not only information on EAT volume, but also on its density. Indeed, EAT density reflected by the recently developed fat attenuation index (FAI) is emerging as a useful index of PCAT inflammation, PAAT inflammation and fibrosis, while the relevance of density of PVentAT is much less known. The emerging data indicates that FAI can be an important diagnostic and prognostic tool in both coronary artery disease and atrial fibrillation. Future studies will demonstrate if it also could be used as a marker of efficacy of therapies and whether FAI PVentAT could indicate ventricular pathologies, such as heart failure. The aim of the review is to present computed tomography derived FAI as an important tool both to study and better understand the epicardial fat and as a potential predictive marker in cardiovascular disorders.

Muscle atrophy and weakness are prevalent features of cancer. Although extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naive cancer. Herein, orthotopic, syngeneic models of epithelial ovarian cancer and pancreatic ductal adenocarcinoma, and a patient-derived pancreatic xenograft model, were used to define the impact of malignancy on cardiac structure, function, and metabolism. Tumor-bearing mice developed cardiac atrophy and intrinsic systolic and diastolic dysfunction, with arterial hypotension and exercise intolerance. In hearts of ovarian tumor-bearing mice, fatty acid-supported mitochondrial respiration decreased, and carbohydrate-supported respiration increased-showcasing a substrate shift in cardiac metabolism that is characteristic of heart failure. Epithelial ovarian cancer decreased cytoskeletal and cardioprotective gene expression, which was paralleled by down-regulation of transcription factors that regulate cardiomyocyte size and function. Patient-derived pancreatic xenograft tumor-bearing mice show altered myosin heavy chain isoform expression-also a molecular phenotype of heart failure. Markers of autophagy and ubiquitin-proteasome system were upregulated by cancer, providing evidence of catabolic signaling that promotes cardiac wasting. Together, two cancer types were used to cross-validate evidence of the structural, functional, and metabolic cancer-induced cardiomyopathy, thus providing translational evidence that could impact future medical management strategies for improved cancer recovery in patients.

Endothelial dysfunction (ED) is defined as an impairment in the vasodilatory, anti-thrombotic, and anti-inflammatory properties of the cells that make up the lining of blood vessels. ED is considered a key step in the development of atherosclerotic cardiovascular disease. The association between ED and systemic inflammatory diseases is well established. However, the prevalence and clinical significance of ED in psoriatic arthritis (PsA) have been investigated to a lesser extent. This review aims to explore the link between ED and PsA, including ED in macro- and microcirculation, as well as risk factors for its occurrence in PsA and its relationship with atherosclerosis in PsA. Furthermore, the ED in PsA was compared with that of rheumatoid arthritis (RA). Regarding ED in the microcirculation, the coronary flow reserve was found to be significantly reduced in individuals with PsA. The relationship between PsA and macrovascular ED is more pronounced, along with more advanced atherosclerosis detected in patients with PsA. These results are consistent with those obtained in RA studies. On the other hand, arterial stiffness and signs of vascular remodeling were found more frequently in RA than in PsA, with the potential role of efficient anti-TNF treatment in patients with PsA and psoriasis explaining this finding. The impact of ED on cardiovascular diseases and the burden of this risk caused independently by PsA have not yet been precisely established, however, this group of patients requires special attention with regard to cardiovascular events.

Preserved ejection fraction heart failure and obesity frequently coexist. Whether obesity plays a consistent role in the pathogenesis of preserved ejection fraction heart failure is unclear. Accumulation of visceral adiposity underlies the pathogenic aftermaths of obesity. However, visceral adiposity imaging is assessed by computed tomography or magnetic resonance and thus not routinely available. In contrast, epicardial adiposity thickness is assessed by echocardiography and thus routinely available. We review the rationale for assessing epicardial adiposity thickness in patients with preserved ejection fraction heart failure and elevated body mass index.

Body mass index correlates poorly with visceral, and epicardial adiposity. Visceral and epicardial adiposity enlarges as preserved ejection fraction heart failure progresses. Epicardial adiposity may hasten the progression of coronary artery disease and impairs left ventricular sub-endocardial perfusion and diastolic function. Epicardial adiposity thickness may help monitor the therapeutic response in patients with preserved ejection failure heart failure and elevated body mass index.

Diabetic cardiomyopathy (DCM) represents one of the typical complications associated with diabetes. It has been described as anomalies in heart function and structure, with consequent high morbidity and mortality. DCM development can be described by two stages; the first is characterized by left ventricular hypertrophy and diastolic dysfunction, and the second by heart failure (HF) with systolic dysfunction. The proposed mechanisms involve cardiac inflammation, advanced glycation end products (AGEs) and angiotensin II. Furthermore, different studies have focused their attention on cardiomyocyte death through the different mechanisms of programmed cell death, such as apoptosis, autophagy, necrosis, pyroptosis and ferroptosis. Exosome release, adipose epicardial tissue and aquaporins affect DCM development. This review will focus on the description of the mechanisms involved in DCM progression and development.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

Epicardial adipose tissue (EAT) detected by computed tomography (CT) is associated with morbidity and mortality in patients with COVID-19 and other critical care patient cohorts, whereas their prognostic relevance in trauma patients remains unclear. The present study explored associations with four potential short-term outcomes in trauma patients.

All consecutive trauma patients requiring emergency tracheal intubation and mechanical ventilation before initial whole-body CT imaging at a level-1 trauma center over a 12-year period (2008-2019) were reanalyzed for this study. EAT was measured semiquantitatively in initial CT and analyzed regarding associations with 24-hour and 30-day mortality using Cox proportional hazard models. In survivors, associations of EAT with intensive care unit length of stay (ICU LOS) and mechanical ventilation duration were analyzed using linear regression analyses.

Four hundred fifty-five patients (74.7% male) with a median age of 49 years, and a median injury severity score (ISS) of 26 points were analyzed. In univariable analysis, EAT index was significantly associated with 24-hour and 30-day mortality (p = 0.007, and p = 0.013, respectively). After adjustment for significant predictors age, body mass index, and ISS, no significant associations were confirmed (p = 0.622, and p = 0.903, respectively). In a subanalysis of 353 survivors, EAT index was significantly associated with ICU LOS and mechanical ventilation duration in univariable analyses (p = 0.031, and p = 0.014, respectively), but not in multivariable analyses (p = 0.81 and p = 0.46, respectively).

EAT index was associated with short-term outcomes in severely injured trauma patients, which not remained significant in multivariable analysis, suggesting that its prognostic capability is limited.

Recent research into laminopathic lipodystrophies-rare genetic disorders caused by mutations in the LMNA gene-has greatly expanded our knowledge of their complex pathology and metabolic implications. These disorders, including Hutchinson-Gilford progeria syndrome (HGPS), Mandibuloacral Dysplasia (MAD), and Familial Partial Lipodystrophy (FPLD), serve as crucial models for studying accelerated aging and metabolic dysfunction, enhancing our understanding of the cellular and molecular mechanisms involved. Research on laminopathies has highlighted how LMNA mutations disrupt adipose tissue function and metabolic regulation, leading to altered fat distribution and metabolic pathway dysfunctions. Such insights improve our understanding of the pathophysiological interactions between genetic anomalies and metabolic processes. This review merges current knowledge on the phenotypic classifications of these diseases and their associated metabolic complications, such as insulin resistance, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome, all of which elevate the risk of cardiovascular disease, stroke, and diabetes. Additionally, a range of published therapeutic strategies, including gene editing, antisense oligonucleotides, and novel pharmacological interventions aimed at addressing defective adipocyte differentiation and lipid metabolism, will be explored. These therapies target the core dysfunctional lamin A protein, aiming to mitigate symptoms and provide a foundation for addressing similar metabolic and genetic disorders.

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure.

26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed.

SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects.

Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

Leucine is involved in promoting fatty acid oxidation and lipolysis, mediating lipid metabolism and energy homeostasis, thus it has been widely used in livestock production. However, the effects of leucine on fat deposition and nutrition in Shaziling pigs remain unclear. A total of 72 Shaziling pigs (150 days old, weight 35.00 ± 1.00 kg) were randomly divided into 2 groups and fed with basal diet (control group) or basal diet containing 1% leucine (leucine group) for 60 days. The results showed that leucine significantly increased the average daily feed intake but decreased the ratio of feed to gain (P < 0.05), increased the loin muscle area and serum glucose content (P < 0.05) of Shaziling pigs. Besides, leucine regulated the re-distribution of fatty acids from adipose tissue to muscle as it significantly increased the contents of C18:1n-9 and C22:6n-3 (DHA) in the longissimus thoracis while decreased the contents of C22:5n-3 (DPA), C20:5n-3 (EPA), and DHA in the adipose tissue of Shaziling pigs (P < 0.05). Lipidomic analysis showed that the contents of phosphatidylethanolamines (PEs), cardiolipins (CLs), and phosphatidylglycerols (PGs) in the longissimus thoracis and the contents of lysophosphatidylethanolamines (LPEs), ceramides (Cers), phosphatidylinositols (PIs) in adipose tissue of Shaziling pigs were decreased in leucine group (P < 0.05). Collectively, this study clarified that dietary addition of 1% leucine have a better effect on growth performance and the deposition of beneficial fatty acids in the muscle of Shaziling pigs, which is conductive to the production of high quality and healthy pork. In addition, leucine altered the lipid composition of muscle and fat in Shaziling pigs. The related results provide a theoretical basis and application guidance for regulating fat deposition in Shaziling pigs, which is important for the healthy breeding of Shaziling pigs.

Based on the available modern medical literature, the article summarizes data on the morpho-functional significance of epicardial adipose tissue (EAT) in health and heart failure, analyzes the likelihood and reliability of the formation of the obesity paradox, and also discusses its possible morpho-functional mechanisms. The authors reviewed and analyzed the consequences of the obesity paradox in the aspect of the normal EAT phenotype protectivity. The review proposed ways of further research in this direction aimed at a deep anatomical and physiological analysis and at determining the morpho-functional role of EAT in the adaptive mechanisms of myocardial trophic provision, which may be an important part of the pathogenetic connection between obesity and CHF and, therefore, can improve outcomes in such patients.

Accumulating evidence suggests that ectopic/visceral adiposity may play a key role in the pathogenesis of nonischaemic cardiovascular diseases associated with type 2 diabetes. Epicardial adipose tissue (EAT) is a complex visceral fat depot, covering 80% of the cardiac surface with anatomical and functional contiguity to the myocardium and coronary arteries. EAT interacts with the biology of the underlying myocardium by secreting a wide range of adipokines. Magnetic resonance imaging (MRI) is the reference modality for structural and functional imaging of the heart. The technique is now also emerging as the reference imaging modality for EAT quantification. With this narrative review, we (a) surveyed contemporary clinical studies that utilized cardiovascular MRI to characterize EAT (studies published 2010-2023); (b) listed the clinical trials monitoring the response to treatment in EAT size as well as myocardial functional and structural parameters and (c) discussed the potential pathophysiological role of EAT in the development of diabetic cardiomyopathy. We concluded that increased EAT quantity and its inflammatory phenotype correlate with early signs of left ventricle dysfunction and may have a role in the pathogenesis of cardiac disease in diabetes with and without coronary artery disease.

Cardiac computed tomography angiography (CCTA) is considered the standard non-invasive tool to rule-out obstructive coronary artery disease (CAD). Moreover, several imaging biomarkers have been developed on cardiac-CT imaging to assess global CAD severity and atherosclerotic burden, including coronary calcium scoring, the segment involvement score, segment stenosis score and the Leaman-score. Myocardial perfusion imaging enables the diagnosis of myocardial ischemia and microvascular damage, and the CT-based fractional flow reserve quantification allows to evaluate non-invasively hemodynamic impact of the coronary stenosis. The texture and density of the epicardial and perivascular adipose tissue, the hypodense plaque burden, the radiomic phenotyping of coronary plaques or the fat radiomic profile are novel CT imaging features emerging as biomarkers of inflammation and plaque instability, which may implement the risk stratification strategies. The ability to perform myocardial tissue characterization by extracellular volume fraction and radiomic features appears promising in predicting arrhythmogenic risk and cardiovascular events. New imaging biomarkers are expanding the potential of cardiac CT for phenotyping the individual profile of CAD involvement and opening new frontiers for the practice of more personalized medicine.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.

Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 48 ± 3 months old) to 25% of the control for two weeks and evaluated the effects on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, the monkeys exhibited decreases in bone marrow erythropoiesis (e.g., decreases in reticulocytes and bone marrow erythrocytes), as well as glycogenesis induction (e.g., increase in aspartate aminotransferase (AST)) and malnutrition (e.g., decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test articles that simultaneously induce food intake reduction.

The perception of adipose tissue as a metabolically quiescent tissue, primarily responsible for lipid storage and energy balance (with some endocrine, thermogenic, and insulation functions), has changed. It is now accepted that adipose tissue is a crucial regulator of metabolic health, maintaining bidirectional communication with other organs including the cardiovascular system. Additionally, adipose tissue depots are functionally and morphologically heterogeneous, acting not only as sources of bioactive molecules that regulate the physiological functioning of the vasculature and myocardium but also as biosensors of the paracrine and endocrine signals arising from these tissues. In this way, adipose tissue undergoes phenotypic switching in response to vascular and/or myocardial signals (proinflammatory, profibrotic, prolipolytic), a process that novel imaging technologies are able to visualize and quantify with implications for clinical prognosis. Furthermore, a range of therapeutic modalities have emerged targeting adipose tissue metabolism and altering its secretome, potentially benefiting those at risk of cardiovascular disease.

(1) Background: Epicardial adipose tissue influences cardiac biology in physiological and pathological terms. As it is suspected to be linked to coronary artery calcification, identifying improved methods of diagnostics for these patients is important. The use of radiomics and the new Photon-Counting computed tomography (PCCT) may offer a feasible step toward improved diagnostics in these patients. (2) Methods: In this retrospective single-centre study epicardial adipose tissue was segmented manually on axial unenhanced images. Patients were divided into three groups, depending on the severity of coronary artery calcification. Features were extracted using pyradiomics. Mean and standard deviation were calculated with the Pearson correlation coefficient for feature correlation. Random Forest classification was applied for feature selection and ANOVA was performed for group comparison. (3) Results: A total of 53 patients (32 male, 21 female, mean age 57, range from 21 to 80 years) were enrolled in this study and scanned on the novel PCCT. "Original_glrlm_LongRunEmphasis", "original_glrlm_RunVariance", "original_glszm_HighGrayLevelZoneEmphasis", and "original_glszm_SizeZoneNonUniformity" were found to show significant differences between patients with coronary artery calcification (Agatston score 1-99/≥100) and those without. (4) Conclusions: Four texture features of epicardial adipose tissue are associated with coronary artery calcification and may reflect inflammatory reactions of epicardial adipose tissue, offering a potential imaging biomarker for atherosclerosis detection.

The interconnection between cardiac function and circadian rhythms is of great importance. While the role of the biological clock gene Timeless (Tim) in circadian rhythm has been extensively studied, its impact on cardiac function remains largely been unexplored. Previous research has provided experimental evidence for the regulation of the heart by adipose tissue and the targeting of miR-276a/b on Timeless. However, the extent to which adipose tissue regulates cardiac Timeless genes trans-organically through miR-276a/b, and subsequently affects cardiac function, remains uncertain. Therefore, the objective of this study was to investigate the potential trans-organ modulation of the Timeless gene in the heart by adipose tissue through miR-276a/b. We found that cardiac-specific Timeless knockdown and overexpression resulted in a significant increase in heart rate (HR) and a significant decrease in Heart period (HP), diastolic intervals (DI), systolic intervals (SI), diastolic diameter (DD), and systolic diameter (SD). miR-276b systemic knockdown resulted in a significant increase in DI, arrhythmia index (AI), and fractional shortening (FS) significantly increased and SI, DD and SD significantly decreased. Adipose tissue-specific miR-276a/b knockdown and miR-276a overexpression resulted in a significant increase in HR and a significant decrease in DI and SI, which were improved by exercise intervention. This study presents a novel finding that highlights the significance of the heart circadian clock gene Timeless in heart function. Additionally, it demonstrates that adipose tissue exerts trans-organ modulation on the expression of the heart Timeless gene via miR-276a/b.

Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutaneous AT represents a more classical energy storage depot. Perivascular adipose tissue (PVAT) regulates vascular biology via paracrine cross-talk signals. In this position paper, the state-of-the-art knowledge of various AT depots is reviewed providing a consensus definition of PVAT around the coronary arteries, as the AT surrounding the artery up to a distance from its outer wall equal to the luminal diameter of the artery. Special focus is given to the interactions between PVAT and the vascular wall that render PVAT a potential therapeutic target in cardiovascular diseases. This Clinical Consensus Statement also discusses the role of PVAT as a clinically relevant source of diagnostic and prognostic biomarkers of vascular function, which may guide precision medicine in atherosclerosis, hypertension, heart failure, and other cardiovascular diseases. In this article, its role as a 'biosensor' of vascular inflammation is highlighted with description of recent imaging technologies that visualize PVAT in clinical practice, allowing non-invasive quantification of coronary inflammation and the related residual cardiovascular inflammatory risk, guiding deployment of therapeutic interventions. Finally, the current and future clinical applicability of artificial intelligence and machine learning technologies is reviewed that integrate PVAT information into prognostic models to provide clinically meaningful information in primary and secondary prevention.

Epicardial adipose tissue (EAT) is increasingly being recognized as a determinant of myocardial biology. The EAT-heart crosstalk suggests causal links between dysfunctional EAT and cardiomyocyte impairment. Obesity promotes EAT dysfunction and shifts in secreted adipokines which adversely affect cardiac metabolism, induce cardiomyocyte inflammation, redox imbalance and myocardial fibrosis. Thus, EAT determines cardiac phenotype via effects on cardiac energetics, contractility, diastolic function, and atrial conduction. Vice-versa the EAT is altered in heart failure (HF), and such phenotypic changes can be detected by noninvasive imaging or incorporated in Artificial Intelligence-enhanced tools to aid the diagnosis, subtyping or risk prognostication of HF. In the present article, we summarize the links between EAT and the heart, explaining how the study of epicardial adiposity can improve the understanding of cardiac disease, serve as a source of diagnostic and prognostic biomarkers, and as a potential therapeutic target in HF to improve clinical outcomes.