Search Results (110)

The most frequently used laboratory animals for studies on adipose tissue properties and obesity are rodents. However, there are significant differences in the types of visceral fat depots between rodents and humans, including fat depots in the heart area. The large human fat depot of greatest interest in cardiac research is the epicardial adipose tissue (EAT). Its properties are widely investigated, because the EAT lies directly on the heart’s surface and can easily affect myocardial physiology. The major fat depot in rodents‘ chest—pericardial fat—is located on the ventral surface of the parietal lamina of the pericardium and is often incorrectly referred to as the EAT. Further confusion arises from reports claiming that rodents are entirely devoid of the EAT. We decided to verify adipose tissues in the heart area of 16 male Sprague Dawley rats under physiological conditions and in obesity. The animals in the NFD group (n = 8) were fed with a standard diet while these in the HFD group (n = 8) were fed with a high-fat diet (31% fat) starting from 4 weeks after birth. When the animals reached 12 weeks, the presence of fat deposits was verified. Additionally, their blood was collected to characterize carbohydrate and lipid metabolism changes, adipokine profile alterations, and their systemic inflammation status. The obesogenic diet caused significant disturbances in their carbohydrate and lipid metabolism, as well as hyperleptinemia. A high-fat diet primarily promoted the accumulation of pericardial fat, which was absent in the NFD rats and observed in 6 out of the 8 HFD animals. In both groups, adipocytes were also found directly on the hearts’ surfaces (EAT), albeit in very small numbers and limited to the atrioventricular groove on the dorsal side of the hearts. These adipocytes were dispersed among the vessels, making quantitative assessment and separation difficult, however, macroscopic evaluation revealed no noticeable differences in its extent. In conclusion, although rats are not entirely devoid of the EAT, their suitability for studying the properties of the EAT appears to be considerably limited. Full article

Background: Type 2 diabetes (T2D patients) have a 74% increased risk of heart failure (HF), but traditional HF biomarkers lack sensitivity in early disease detection. Increased epicardial adipose tissue volume (EATv) is associated with cardiovascular risk in T2D, and novel biomarkers such as growth differentiation factor 15 (GDF15), Galectin-3, and soluble suppression of tumorigenicity 2 (sST2) are inflammation biomarkers linked to HF. Methods: We investigated associations between EATv, inflammation biomarkers, and the effect of metabolic control in 14 healthy controls (HCs) and 36 newly diagnosed T2D patients both before (poor glycemic control, PGC) and after 12 months of glycemic optimization (good glycemic control, GGC). EATv indexed to body surface area (iEATv) was quantified by multidetector computed tomography, and biomarker levels were measured by immunoassays. Results: PGC patients had higher iEATv (59.53 ± 21.67 vs. 36.84 ± 16.57 cm³/m², p = 0.0017) and elevated GDF15, Galectin-3, and sST2 levels (all p < 0.05) than HC subjects. The glycemic optimization reduced iEATv (p = 0.0232) and sST2 (p = 0.048), while GDF15 and Galectin-3 remained unchanged. Multivariable analysis confirmed independent associations between iEATv, GDF15 (β = 0.27, p = 0.027) and sST2 (β = 0.29, p = 0.02). Conclusions: These results support the link between systemic inflammation, EAT expansion, and cardiac dysfunction, and they point to the role of epicardial fat in early HF risk of T2D patients. Full article

Muscle loss unresponsive to nutritional supplementation affects up to 80% of cancer patients and severely reduces survival and treatment response. Exercise may help preserve muscle mass and function, yet the translatability of preclinical methods remains questionable. This study aimed to assess how voluntary wheel running, a clinically relevant physical activity, protects skeletal and cardiac muscle against cancer-mediated dysfunction and identify underlying molecular mechanisms. Methods: BALB/c mice were assigned to sedentary nontumor-bearing (SED+NT), sedentary tumor-bearing (SED+T), wheel run nontumor-bearing (WR+NT), and wheel run tumor-bearing (WR+T). Tumor-bearing groups received 5 × 10⁵ C26 cells; WR mice had wheel access for 4 weeks. Muscle function and tissue were analyzed for protective mechanisms. Results: SED+T mice exhibited significant fat and lean mass loss, indicating cachexia, which was prevented in WR+T mice. SED+T also showed 15% reduced grip strength and cardiac dysfunction, while WR+T preserved function. WR+T mice had lower expression of muscle wasting markers (Atrogin1, MuRF1, GDF15, GDF8/11). Physical activity also reduced tumor mass by 57% and volume by 37%. Conclusion: Voluntary wheel running confers tumor-suppressive, myoprotective, and cardioprotective effects. These findings support physical activity as a non-pharmacological strategy to combat cancer-related muscle wasting and dysfunction. Full article

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic disorder, often coexisting with chronic obstructive pulmonary disease (COPD). This study aims to identify the shared pathogenic mechanisms between HFpEF and COPD and validate them in an experimental HFpEF model. Transcriptomic datasets from HFpEF cardiac tissue and COPD lung tissue were analyzed using differentially expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and functional enrichment analysis. Key genes were identified through least absolute shrinkage and selection operator (LASSO) regression. Immune cell infiltration was assessed using xCell and CIBERSORT, and single-cell RNA sequencing (scRNA-seq) was utilized to determine gene expression patterns across different cell populations. A high-fat diet and N[w]-nitro-L-arginine methyl ester (L-NAME)-induced HFpEF mouse model was established, and the expression of SESN3 and autophagy-related markers was evaluated in both cardiac and pulmonary tissues using immunofluorescence, quantitative PCR (qPCR), Western blotting (WB), and transmission electron microscopy. DEG and WGCNA analyses identified 1243 and 131 core genes in HFpEF and COPD, respectively. Functional enrichment analysis highlighted autophagy as a common regulatory pathway in both conditions. Among the nine intersecting genes, SESN3 was identified as a key candidate through LASSO regression. Immune infiltration analysis and scRNA-seq further demonstrated the involvement of SESN3 in both cardiac and pulmonary pathophysiology. In vivo experiments showed that HFpEF mice exhibited significant lung injury. Furthermore, SESN3 upregulation and autophagy dysregulation were observed in both heart and lung tissues, supporting a potential systemic role of SESN3-mediated autophagy in HFpEF-related pulmonary alterations. This study suggests that SESN3-mediated autophagy may represent a shared mechanism between HFpEF and COPD. Our findings suggest that HFpEF may be associated with pulmonary alterations beyond cardiac dysfunction alone. These results provide novel insights into the potential multi-organ involvement in HFpEF and support the role of SESN3 as a shared molecular target in both cardiac and pulmonary pathologies. Full article

Intercellular interactions among cardiac cell populations are essential for cardiac morphogenesis, yet the molecular mechanisms orchestrating these events remain incompletely understood. Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar cell polarity protein whose function in the developing heart has not been fully elucidated. To address this, we generated a Dchs1-HA knock-in mouse model to define its spatial, temporal, and cellular expression patterns. Using immunohistochemistry, western blotting, and single-cell transcriptomics across developmental stages, we demonstrate that cardiac Dchs1 expression is restricted to non-cardiomyocyte lineages. DCHS1 displays dynamic subcellular localization and tissue organization depending on the developmental timepoint, with staining being found in epicardial and endocardial surfaces at earlier embryonic stages and in the compact myocardium in later fetal and neonatal stages. During fetal and neonatal stages, DCHS1-positive non-myocyte, non-endothelial cells form polarized extensions that bridge endothelial and non-myocyte, non-endothelial cells, suggesting direct heterotypic and homotypic interactions. Western blotting revealed evidence of DCHS1 proteolytic cleavage, with intracellular C-terminal fragments. RNA co-expression with its binding partner FAT4 supports a conserved, non-myocyte-specific DCHS1-FAT4 signaling axis. These findings identify DCHS1 as a potential molecular tether that is utilized in intercellular communications during cardiac development, with implications for congenital and acquired heart disease. Full article

Background: Obesity has been defined as a true worldwide “pandemic” by the World Health Organization and represents one of the major public health problems. It is associated with a reduction in life expectancy of about 7–8 years due to related cardiovascular diseases such as arterial hypertension, metabolic syndrome, insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Adipose tissue is not merely a fat storage site but a true endocrine and immunologically active organ that secretes hormones and mediators (adipokines), influencing cardiovascular risk and host physiology. Objective: This review summarizes the current understanding of the role of epicardial adipose tissue (EAT) in cardiovascular disease pathophysiology and discusses its clinical diagnostic and therapeutic implications. Methods: A narrative non-systematic review was conducted focusing on recent literature concerning the biological and clinical aspects of cardiac adipose tissue, with particular emphasis on epicardial adipose tissue. The review examined its gene expression profile, secretory function, and interaction with cardiovascular structures and diseases. Findings: There are different types of adipose tissue, including cardiac adipose tissue, which comprises epicardial and pericardial (or paracardiac) fractions. Epicardial adipose tissue is unique due to its proximity to the heart and a distinct gene expression profile compared to other adipose depots such as visceral and subcutaneous fat. EAT plays a crucial role in the development and progression of cardiovascular diseases with high morbidity and mortality, acting both as a metabolic and inflammatory mediator. Conclusion: Cardiac adipose tissue, particularly EAT, is a key player in cardiometabolic disease. Understanding its pathophysiological role and incorporating imaging tools to evaluate EAT may enhance cardiovascular risk stratification and disease management. Full article

Epicardial adipose tissue (EAT), strategically located between the myocardium and the visceral pericardial layer, is increasingly recognized as an active player in cardiovascular health rather than a passive fat depot. EAT secretes a notable array of bioactive molecules known as adipokines, which exert critical exocrine and paracrine effects. Recent research has focused on pericoronary adipose tissue (PCAT)—the EAT surrounding coronary arteries—demonstrating its intricate bidirectional relationship with the vascular wall. Under normal physiological conditions, this interaction promotes vascular homeostasis; however, dysfunctional PCAT can release pro-inflammatory adipokines implicated in the pathogenesis of atherogenesis. Notably, PCAT inflammation has emerged as a significant factor associated with the development of coronary artery disease (CAD) and major cardiovascular events. This review seeks to elucidate the imaging methodologies employed to evaluate EAT, emphasizing cardiac computed tomography (CCT) as the preeminent imaging modality. Unlike echocardiography and cardiac magnetic resonance imaging, CCT not only visualizes and quantifies EAT but also concurrently assesses coronary arteries and PCAT. Recent findings have established the potential of CCT-derived PCAT attenuation as a noninvasive biomarker for coronary inflammation, offering prospects for monitoring therapeutic responses to innovative anti-inflammatory interventions in CAD management. Full article

Chagas disease (CD), caused by the protozoan T. cruzi, is a serious public health issue with high morbidity and mortality rates. Approximately 7 million people are infected, mostly in Latin America. The pathogenesis is multifactorial and poorly elucidated, particularly regarding the role of adipose tissue (AT). This review aims to explore the complex relationship between T. cruzi and AT, focusing on the possible role of this tissue in CD, as well as to explore the impact of diet on the progression of the disease. T. cruzi infects adipocytes, affecting their function. Chronic infection alters adipose physiology, contributing to systemic inflammation and metabolic disturbances. Adipokines are dysregulated, while markers of inflammation and oxidative stress increase within AT during CD. Additionally, the immune response and clinical aspects of CD may be influenced by the host’s diet. High-fat diets (HFDs) impact parasite burden and cardiac pathology in murine models. The complex interaction among T. cruzi infection, AT dysfunction, and dietary factors underscore the complexity of CD pathogenesis. Despite accumulating evidence suggesting the role of AT in CD, further research is needed to elucidate its clinical implications. Understanding the bidirectional relationship between AT and T. cruzi infection may offer insights into disease progression and potential therapeutic targets, highlighting the importance of considering adipose physiology in CD management strategies. Full article

Background/Objectives: Cardiac amyloidosis (CA) is associated with amyloid infiltration of the extra-cardiac tissue, which may occur in the early stages of the disease. This study evaluates the diagnostic utility of thoracic fat pad biopsy obtained during a pacemaker or ICD implantation as an alternative to the standard diagnostic criteria for systemic amyloidosis. Methods: This exploratory, retrospective study included 27 patients with suspected or diagnosed CA who underwent pacemaker or defibrillator therapy. Results: Of these, 16 patients were confirmed to have CA (15 with technetium-labeled bisphosphonate bone scintigraphy and 1 with protein electrophoresis and echocardiographic findings) while 11 were confirmed to be CA-negative. The thoracic fat pad biopsy demonstrated a specificity of 100% but a sensitivity of only 31%. Among patients with transthyretin (ATTR)-CA, the sensitivity remained similarly low, at 27%. These results are consistent with prior findings on abdominal fat pad biopsy in ATTR-CA, highlighting the limited diagnostic yield of this method. Conclusions: Thoracic fat pad biopsy cannot be recommended as a standard diagnostic tool for CA, particularly in ATTR-CA, due to its poor sensitivity. However, in AL (amyloid light-chain) amyloidosis, this minimally invasive procedure may aid diagnosis without additional invasive interventions. Full article

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. Full article

This study aimed to investigate the impact of a Western diet and resistance training on cardiac remodeling in a rat model of chemically induced mammary cancer. Fifty-six female Wistar rats were randomly assigned to one of eight experimental groups, evaluating the impact of Western and standard diets, exercise and sedentarism, and the induction of mammary cancer. Mammary cancer was induced via the intraperitoneal administration of N-methyl-N-nitrosourea (MNU) (50 mg/kg) at seven weeks of age. The resistance training protocol consisted of ladder climbing three times per week for an 18-week period, with a gradual increase in load over time. At the end of the 20-week experimental period, the animals were anesthetized and underwent echocardiography. Subsequently, the animals were euthanized, and organs and visceral adipose tissue (VAT) were collected and analyzed. A histopathological examination was performed on the mammary tumors. The Western diet increased relative VAT and contributed to cardiovascular and tumor-related changes, including an increase in interventricular septum thickness (IVS) and left ventricle posterior wall thickness (LVPW) at end-systole. Exercise reduced fat accumulation, improved cardiac performance, and helped regulate cardiovascular function, as indicated by a higher eccentricity index (EI) in the WD+EX group compared to the WD group. The WD was associated with increased VAT accumulation and initially delayed tumor initiation; however, over time, it contributed to bigger tumor aggressiveness. This diet also delayed tumor initiation but increased LVPW. Exercise, when combined with a WD, accelerated tumorigenesis, malignant transformation and invasiveness, resulted in the higher prevalence of invasive tumors. These findings underscore the complex and potentially compounding effects of diet and exercise on cancer progression. Full article

Background: Features of pericoronary adipose tissue (PCAT) from coronary computed tomography angiography (CCTA) are associated with inflammation and cardiovascular risk. As PCAT is vascularly connected with coronary vasculature, the presence of iodine is a potential confounding factor on PCAT HU and textures that has not been adequately investigated. We aim to use dynamic cardiac CT perfusion (CCTP) to understand the perfusion of PCAT and determine its effects on PCAT assessment. Methods: From CCTP, we analyzed HU dynamics of territory-specific PCAT, the myocardium, and other adipose depots in patients with coronary artery disease. HU, blood flow, and radiomics were assessed over time. Changes from peak aorta time, P_a, chosen to model the acquisition time of CCTA, were obtained. Results: HU in PCAT increased more than in other adipose depots. Blood flow in PCAT was ~23% of that in the contiguous myocardium. A two-second offset [before, after] P_a resulted in [4 ± 1.1 HU, 3 ± 1.5 HU] differences in PCAT, giving a 7 HU swing. Due to changes in HU, the apparent PCAT volume reduced by ~15% from the first scan (P₁) to P_a using a conventional fat window. Comparing radiomic features over time, 78% of features changed >10% relative to P₁. Distal and proximal to a significant stenosis, we found less enhancement and longer time-to-peak distally in PCAT. Conclusions: CCTP elucidates blood flow in PCAT and enables the analysis of PCAT features over time. PCAT assessments (HU, apparent volume, and radiomics) are sensitive to acquisition timing and obstructive stenosis, which may confound the interpretation of PCAT in CCTA images. Data normalization may be in order. Full article

The combination of alcohol and a low-carbohydrate, high-protein, high-fat atherogenic diet (AD) increases the risk of lethal arrhythmias in apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice with metabolic dysfunction-associated steatotic liver disease (MASLD). This study investigates whether left ventricular (LV) myocardial interstitial fibrosis (MIF), formed during the progression of metabolic dysfunction-associated steatohepatitis (MASH), contributes to this increased risk. Male AL mice were fed an AD with or without ethanol for 16 weeks, while age-matched AL and wild-type mice served as controls. Liver and heart tissues were analyzed, and susceptibility to lethal arrhythmias was assessed through histopathology, fluorescence immunohistochemistry, RNA-Seq, RT-PCR, and lethal arrhythmia-evoked test. Ethanol combined with an AD significantly induced LV MIF in MASH-affected AL mice, as shown by increased fibrosis-related gene expression, Sirius-Red staining, and elevated collagen 1a1 and 3a1 mRNA levels, alongside a higher incidence of lethal arrhythmias. Cardiac myofibroblasts exhibited sympathetic activation and produced elevated levels of fibrosis-promoting factors. This study highlights the role of cardiac myofibroblasts in LV MIF, contributing to an increased incidence of lethal arrhythmias in MASH-affected AL mice fed ethanol and AD, even after the alcohol was fully metabolized on the day of consumption. Full article

Obesity, influenced by environmental pollutants, can lead to complex metabolic disruptions. This systematic review and meta-analysis examined the molecular mechanisms underlying metabolically abnormal obesity caused by exposure to a high-fat diet (HFD) and fine particulate matter (PM_2.5). Following the PRISMA guidelines, articles from 2019 to 2024 were gathered from Scopus, Web of Science, and PubMed, and a random-effects meta-analysis was performed, along with subgroup analyses and pathway enrichment analyses. This study was registered in the Open Science Framework. Thirty-three articles, mainly case–control studies and murine models, were reviewed, and they revealed that combined exposure to HFD and PM_2.5 resulted in the greatest weight gain (82.835 g, p = 0.048), alongside increases in high-density lipoproteins, insulin, and the superoxide dismutase. HFD enriched pathways linked to adipocytokine signaling in brown adipose tissue, while PM_2.5 impacted genes associated with fat formation. Both exposures downregulated protein metabolism pathways in white adipose tissue and activated stress-response pathways in cardiac tissue. Peroxisome proliferator-activated receptor and AMP-activated protein kinase signaling pathways in the liver were enriched, influencing non-alcoholic fatty liver disease. These findings highlight that combined exposure to HFD and PM_2.5 amplifies body weight gain, oxidative stress, and metabolic dysfunction, suggesting a synergistic interaction with significant implications for metabolic health. Full article

Heart failure with preserved ejection fraction (HFpEF) is increasing at an alarming rate worldwide, with limited effective therapeutic interventions in patients. Sudden cardiac death (SCD) and ventricular arrhythmias present substantial risks for the prognosis of these patients. Obesity is a risk factor for HFpEF and life-threatening arrhythmias. Obesity and its associated metabolic dysregulation, leading to metabolic syndrome, are an epidemic that poses a significant public health problem. More than one-third of the world population is overweight or obese, leading to an enhanced risk of incidence and mortality due to cardiovascular disease (CVD). Obesity predisposes patients to atrial fibrillation and ventricular and supraventricular arrhythmias—conditions that are caused by dysfunction in the electrical activity of the heart. To date, current therapeutic options for the cardiomyopathy of obesity are limited, suggesting that there is considerable room for the development of therapeutic interventions with novel mechanisms of action that will help normalize sinus rhythms in obese patients. Emerging candidates for modulation by obesity are cardiac ion channels and Ca-handling proteins. However, the underlying molecular mechanisms of the impact of obesity on these channels and Ca-handling proteins remain incompletely understood. Obesity is marked by the accumulation of adipose tissue, which is associated with a variety of adverse adaptations, including dyslipidemia (or abnormal systemic levels of free fatty acids), increased secretion of proinflammatory cytokines, fibrosis, hyperglycemia, and insulin resistance, which cause electrical remodeling and, thus, predispose patients to arrhythmias. Furthermore, adipose tissue is also associated with the accumulation of subcutaneous and visceral fat, which is marked by distinct signaling mechanisms. Thus, there may also be functional differences in the effects of the regional distribution of fat deposits on ion channel/Ca-handling protein expression. Evaluating alterations in their functional expression in obesity will lead to progress in the knowledge of the mechanisms responsible for obesity-related arrhythmias. These advances are likely to reveal new targets for pharmacological modulation. Understanding how obesity and related mechanisms lead to cardiac electrical remodeling is likely to have a significant medical and economic impact. Nevertheless, substantial knowledge gaps remain regarding HFpEF treatment, requiring further investigations to identify potential therapeutic targets. The objective of this study is to review cardiac ion channel/Ca-handling protein remodeling in the predisposition to metabolic HFpEF and arrhythmias. This review further highlights interleukin-6 (IL-6) as a potential target, cardiac bridging integrator 1 (cBIN1) as a promising gene therapy agent, and leukotriene B4 (LTB4) as an underappreciated pathway in future HFpEF management. Full article