Search Results (103)

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article

Background: Coronary artery calcium (CAC) scores are a widely used surrogate marker for atherosclerotic burden, but they do not fully reflect plaque vulnerability or coronary inflammation. This study aimed to evaluate the relationship between CACs, coronary plaque characteristics, and perivascular inflammatory activity using advanced CCTA and CaRi-Heart^® analysis. Methods: A total of 250 patients with no prior cardiovascular disease were retrospectively evaluated and stratified by CACs into three groups: 0 (n = 28), 1–100 (n = 121), and >100 (n = 101). Coronary plaque morphology, high-risk plaque (HRP) features, CAD-RADS scores, and AI-derived fat attenuation index (FAI) centiles were assessed. Results: Significant differences across CAC categories were observed for several key parameters. The number of diseased coronary segments increased markedly (from 1.39 ± 1.10 vs. 2.97 ± 1.57 vs. 3.94 ± 2.10; p < 0.0001, one-way ANOVA). A similar upward trend was seen for segment involvement scores, HRP prevalence, and the proportions of mixed and calcified plaque components. Regression analysis demonstrated that CACs correlated significantly with segment burden (r² = 0.2520), CAD-RADS (r² = 0.1352), and the FAI score centile (r² = 0.0568). Conclusions: This study highlights the limitations of CACs as a standalone risk stratification tool. Vulnerable and inflamed plaques may already be present in patients with low or zero CACs. Integrating CCTA with perivascular FAI mapping enables earlier detection of biologically active atherosclerosis and supports more precise clinical decision-making. Full article

Background/Objectives: Atrial fibrillation (AF) is associated with increased epicardial adipose tissue (EAT), atrial dilation, and coronary inflammation, though causality remains unclear. Cardiac computed tomography (CCT) allows for precise quantification of EAT volume and the left atrial volume index (LAVI), along with the calculation of the fat attenuation index (FAI), indicating coronary inflammation. Combined with the Coronary Artery Disease-Reporting and Data System (CAD-RADS), these imaging markers may improve AF risk stratification. This study evaluates the association between peri-atrial EAT volumes, LAVI, CAD-RADS, and FAI scores in AF patients using advanced AI platforms. Methods: This retrospective study analyzed 122 patients presenting with angina-type pain and a low-to-intermediate likelihood of CAD, who underwent CCT. Patients were divided into two groups based on rhythm status: 42 with AF and 80 without AF. Total EAT, left atrial (LA-EAT), and bi-atrial EAT (BA-EAT) volumes were assessed, along with LAV, CAD-RADS classification, and FAI scores measured using CaRi-Heart^® and syngo.via Frontier^®. Results: AF patients exhibited significantly higher EAT volumes (total EAT: 231.8 ± 45.85 vs. 153.2 ± 54.14 mL, p < 0.0001; LA-EAT: 23.55 ± 6.44 vs. 15.54 ± 8.49 mL, p < 0.0001; BA-EAT: 50.24 ± 12.69 vs. 39.84 ± 15.70 mL, p = 0.0002) and elevated LAVI values (57.7 ± 11.44 vs. 45.9 ± 12.58 mL/m², p < 0.0001). ROC analyses confirmed strong diagnostic performance of total EAT (AUC = 0.869), LA-EAT (AUC = 0.776), BA-EAT (AUC = 0.703), and the LAVI (AUC = 0.756). Higher CAD-RADS categories (2–5) were more frequent in AF, although significant differences were observed only in the lowest category (0–1; 26.2% AF vs. 47.8% non-AF, p = 0.032). Total FAI scores were also higher in AF patients (14.83 ± 10.16 vs. 12.37 ± 7.89, p = 0.044). Conclusions: Increased EAT volumes, an elevated LAVI, and higher FAI scores are significantly associated with AF, suggesting a combined structural and inflammatory substrate. EAT, the LAVI, the FAI, and CAD-RADS collectively represent valuable non-invasive imaging biomarkers for early AF risk assessment. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Ultrasound attenuation imaging (ATI) is a non-invasive method for quantifying hepatic steatosis, offering advantages over the hepatorenal index (HRI). However, its reliability can be influenced by factors such as measurement depth, ROI size, and subcutaneous fat. This paper examines the impact of these confounders on ATI measurements and discusses diagnostic considerations. In this study, 33 healthy adults underwent liver ultrasound with ATI and HRI protocols. ATI measurements were taken at depths of 2–5 cm below the liver capsule using small and large ROIs. Two operators performed the measurements, and inter-operator variability was assessed. Subcutaneous fat thickness was measured to evaluate its influence on attenuation values. The ATI measurements showed a consistent decrease in attenuation coefficient values with increasing depth, approximately 0.05 dB/cm/MHz. Larger ROI sizes increased measurement variability due to greater anatomical heterogeneity. HRI values correlated weakly with ATI and were influenced by operator technique and subcutaneous fat, the latter accounting for roughly 2.5% of variability. ATI provides a quantitative assessment of hepatic steatosis compared to HRI, although its accuracy can vary depending on the depth and ROI selection. Standardised imaging protocols and AI tools may improve reproducibility and clinical utility, supporting advancements in ultrasound-based liver diagnostics for better patient care. Full article

Cardiovascular disease remains the leading global cause of mortality, with inflammation now recognized as a central driver of atherosclerosis and other cardiometabolic conditions. Recent advances have repositioned perivascular adipose tissue from a passive structural element to an active endocrine and immunomodulatory organ, now a key focus in cardiovascular and metabolic research. Among the most promising tools for assessing perivascular adipose tissue inflammation is the fat attenuation index, a non-invasive imaging biomarker derived from coronary computed tomography angiography. This review explores the translational potential of the fat attenuation index for cardiovascular risk stratification and treatment monitoring in both coronary artery disease and systemic inflammatory or metabolic conditions (psoriasis, systemic lupus erythematosus, inflammatory bowel disease, obesity, type 2 diabetes, and non-obstructive coronary syndromes). We summarize evidence linking perivascular adipose tissue dysfunction to vascular inflammation and adverse cardiovascular outcomes. Clinical studies reviewing the fat attenuation index highlight its ability to detect subclinical inflammation and monitor treatment response. As research advances, standardization of measurement protocols and imaging thresholds will be essential for routine clinical implementation. Full article

Background/Objectives: Obesity is a key driver of cardiovascular disease (CVD), with central adiposity directly involved in adverse cardiac remodeling. Body mass index (BMI) is limited in capturing fat distribution and associated cardiovascular risk. Novel anthropometric indices, including A Body Shape Index (ABSI) and Body Roundness Index (BRI), may offer greater clinical value, but their relationship with electrocardiographic markers of left ventricular hypertrophy (LVH) remains underexplored. This study aims to assess the correlation between novel adiposity indices (ABSI and BRI) and electrocardiographic evidence of LVH, as measured by the Sokolow-Lyon Index (SLI), in individuals with arterial hypertension. Methods: 274 hypertensive patients were recruited, and BMI, ABSI, and BRI were calculated. LVH was assessed via SLI on 12-lead ECG. Participants were stratified by the SLI (≤35 mm vs. >35 mm) for statistical analyses. Results: Patients with a lower SLI showed significantly higher values of ABSI and BRI compared to those in higher SLI group, without differences in BMI. In the entire population, SLI was significantly and inversely correlated with both ABSI (r = −0.296, p < 0.001) and BRI (r = −0.238, p < 0.01), but not with BMI. Multivariate regression analysis confirmed ABSI (p = 0.013) and BRI (p = 0.038) as independent predictors of SLI, even after adjusting for age, blood pressure, renal function, and metabolic parameters. Conclusions: ABSI and BRI are inversely and independently associated with ECG-derived SLI in hypertensive individuals, suggesting that central adiposity may attenuate ECG voltages and obscure LVH detection. Incorporating novel adiposity indices into ECG interpretation may enhance diagnostic accuracy and risk stratification in obese and hypertensive populations. Longitudinal studies are needed to validate these findings and refine clinical algorithms. Full article

Background/Objectives: The amino acid γ-aminobutyric acid (GABA) is the primary neurotransmitter in the central nervous system (CNS) and acts as an autocrine and/or paracrine signaling molecule in various types of non-neuronal cells. On the other hand, GABA is a nutrient found in a variety of foods and is marketed as a health supplement based on a growing number of studies reporting health benefits in humans and recuperations in animal models of diseases. The present study sought to examine whether supplementation of GABA to young mice regulates their growth as well as glucose and lipid metabolism during physiological adolescence. Methods: Mice were supplemented with GABA over a 16-week period with subsequent anthropometric, metabolic, and endocrine measurements. Results: Results showed that 16-week oral supplementation of GABA increased food consumption and body length while attenuating weight gain in male mice but not females. In addition, GABA treatment lowered the index of body fat (Lee index) and increased the expression of lipolytic enzymes in adipose and liver tissues of male mice without affecting blood glucose levels. Remarkably, supplementation of GABA significantly increased the protein expression of growth hormone (GH) in the pituitary gland of both male and female mice. However, it only substantially increased GH levels in the sera of male mice but not females. Moreover, GABA significantly increased the expression of the GH secretagogue peptide ghrelin in the stomachs of male mice only. Conclusions: Together these novel findings suggest that long-term GABA supplementation fundamentally influences the growth and lipid metabolism of males during adolescent development by stimulating ghrelin–GH production and secretion. The mechanisms of GABA-induced sex-dependent upregulations of ghrelin and GH, as well as lipid metabolism in adolescence, await further studies. Full article

Objectives: This study aimed to test the extra-thyroidal impacts of maternal serum iodine concentrations (SICs) on metabolic factors and subsequent pregnancy outcomes. Methods: Single pregnant women aged 18–49 years were recruited during their first prenatal visits. SICs at first trimester (T1) were tested by ICP-MS. Metabolic factors [body mass index (BMI), fat %, glucose, lipids, uric acid, and blood pressure] were measured, and composite indices [the triglyceride–glucose (TyG) index, TyG-BMI, and the Framingham steatosis index (FSI)] were estimated. Obstetric and birth outcomes were retrieved from the hospital information system, including gestational diabetes (GDM), gestational hypertension (GH), fetal distress, postpartum hemorrhage, premature rupture of membrane, small and large for gestational age (SGA and LGA), preterm birth, and low birth weight. Multivariable linear and logistic regression models were applied to explore the associations between maternal SIC, metabolic factors, and pregnancy outcomes. Results: A total of 1456 mothers were included for analysis. Maternal LgSIC values at T1 were inversely associated with early gestational weight gain (β = −0.113, p < 0.001) and BMI at T1 (β = −0.070, p = 0.006), but they were positively associated with triglycerides (β = 0.142, p < 0.001), the TyG index (β = 0.137, p < 0.001), and uric acid (β = 0.060, p = 0.018). However, upon further adjustment for thyroid hormones, the associations were attenuated. The joint effects of high SIC and metabolic conditions (hyperlipidemia, high FSI, and GH) suggested increased adverse pregnancy outcomes (increased postpartum bleeding, reduced birth length, and reduced delivery weeks). Conclusions: Our prospective data in the iodine replete region indicated that high SICs at T1 were associated with increased risk of metabolic conditions and adverse birth outcomes, with the associations being independent of thyroid hormones. Full article

This study investigated whether the supplementation of prebiotic inulin to gestating sows programmatically affects offspring growth performance and meat quality while exploring its epigenetic effects through histone acetylation modulation. After mating, sixty multiparous sows (Landrace × Yorkshire; parity 2–3) were assigned to a 2 × 2 factorial arrangement with inulin (0% vs. 1.5%) and fat (0% or 5%) supplementation until farrowing. Post-weaning, five litters (10 piglets per litter) per treatment were selected and maintained in their original litter for fattening under standardized feeding. The results demonstrated that maternal inulin supplementation during gestation accomplished the following: (1) Increased offspring liver index by 13.4% at weaning and 6.8% at finishing (p < 0.05) while reducing the finishing-phase backfat thickness by 11.6% (p < 0.01), with a significant inulin × fat interaction attenuating fat-induced abdominal lipid accumulation at weaning (p = 0.05). (2) Decreased longissimus dorsi muscle lightness (L*) by 4.5% in finishing pigs (p = 0.02) without altering the other meat quality parameters. (3) Suppressed offspring liver lipid deposition at birth and finishing (p < 0.05), concomitant with upregulated hepatic PGC-1α and CPT1A expression (p < 0.05). (4) Elevated neonatal serum butyrate by 15.6% (p = 0.06) while inhibiting hepatic histone deacetylase (HDAC) activity and enhancing histone H3/H4 acetylation (p < 0.01). These findings suggest that maternal inulin supplementation during gestation mitigates offspring hepatic lipid deposition through butyrate-mediated epigenetic regulation, where microbial-derived butyrate from inulin fermentation inhibits HDAC activity, enhances histone acetylation levels, and upregulates fatty acid β-oxidation gene expression. This study provides novel mechanistic insights into how maternal dietary fiber nutrition programs offspring development through epigenetic reprogramming. Full article

Blood pressure (BP), interarm differences (IAD) in BP, and arterial stiffness (AS) are related to cardiovascular disease risk and are attenuated by exercise training. While active, tennis players (TP) experience bilateral differences in shear stress, and thus vascular function due to the unilateral nature of the sport. However, it is unknown if this translates into attenuated bilateral differences in peripheral blood pressure (pBP), estimated central blood pressure (cBP), and AS, which could provide insight into the local versus systemic effects of exercise training on BP in women. Purpose: to evaluate bilateral differences in pBP, cBP, and AS in Division III female college TP and healthy recreationally active (RA) age- and sex-matched controls. Methods: In a parallel design, TP (n = 10) and RA controls (n = 10) were assessed for anthropometrics, body composition, and bilateral BP measurements using oscillometric cuff technique. Results: TP and RA were well-matched for body weight, body fat percentage, and BMI (all, p > 0.69). Interaction of arm and group, and effects of arm, or group were insignificant for pSBP and pDBP (all, p > 0.137). IAD in pSBP tended lower in TP (p = 0.096, d = 0.8), but IAD in cSBP was lower (p = 0.040, d = 0.8). Augmentation pressure and index were different between arms (p = 0.02), but no interactions (group by arm) were observed (p > 0.05). Conclusions: In groups well-matched for age and body composition, TP tended to have lower BP and IAD in pSBP, but cSBP revealed ~50% lower IAD in TP. Thus, measurement site and exercise training matter when assessing arterial stiffness and interarm differences in BP. Full article

Background: Gut barrier integrity plays a crucial role in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Electroacupuncture (EA) at ST-36 can ameliorate inflammatory responses via stimulating the α7 nicotinic acetylcholine receptor (α7nAChR), but whether EA is effective in preserving the intestinal barrier of MAFLD has not been exactly illustrated. This investigation explored potential protection mechanisms of EA at ST-36 targeting the dismantled gut barrier in MAFLD. Methods: C57BL/6 mice were randomly allocated into several subgroups: control (CON), high-fat diet (HFD), HFD with EA, HFD with EA and α7nAChR inhibitor α-BGT, and HFD with EA and intestinal HO-1 knockout (KO). Body weight, liver weight, visceral fat index, and histopathological examination of the liver and the intestine were determined. Serum biological indexes were evaluated through corresponding kits. Furthermore, the expressions of HO-1, α7nAChR, gut barrier-associated proteins, and the molecular mechanisms in intestinal tissues were assessed via Western blot, RT-qPCR, immunohistology, or immunofluorescence examination. Results: EA treatment decreased body weight, liver weight, and visceral fat index gain and mitigated liver function injury and abnormal lipid indexes, exhibiting less severity of hepatic steatosis, fibrosis, and inflammation responses of MAFLD. Lower gut permeability, less intestinal epithelial disruption, and upregulation of tight junction proteins after EA suggested the protective effects in attenuating intestinal epithelial barrier dysfunction. These protective effects were abolished by α-BGT or intestinal HO-1 deletion. Mechanistically, EA markedly enriched α7nAChR and HO-1 expression and mitigated phosphorylated p38 MAPK/NF-κB activation, which was lost in α-BGT or HO-1 KO treatment. Conclusions: The protective effects of EA at ST-36 in the pathogenesis of MAFLD may be attributed to the preserved intestinal barrier, thereby alleviating systemic inflammatory responses and preventing subsequent liver hits, where the α7nAChR-mediated HO-1/p38 MAPK/NF-κB pathway was crucial to maintain homeostasis. Full article

Background/Objectives: Post-menopausal women are at an increased risk of developing cardiovascular disease. Menaquinone-7 (MK-7) is a fat-soluble vitamin involved in coagulation and maintaining vascular health. The aim of the post hoc analysis of this one-year study is to investigate the effects of MK-7 supplementation on the vascular parameters in pre-, peri-, and post-menopausal women. Methods: In a clinical intervention trial (NCT02404519), a total of 165 women with a low vitamin K status received either 180 µg of MK-7 daily (n = 82) or a matching placebo (n = 83) for one year. Established vascular parameters were measured before and after one year of vitamin K2 supplementation. Pre-, peri-, and post-menopausal women were subdivided according to arterial stiffness, with a high b-stiffness index defined as being greater than the overall median of 9.83. Results: The post hoc analyses showed a significant decrease in desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) plasma levels after MK-7 supplementation (pre/peri, p = 0.009; post, p < 0.001). MK-7 treatment significantly attenuated vascular stiffness in post-menopausal women (placebo +49.1% ± 77.4; MK-7 +9.4% ± 67.1; p = 0.035). Post-menopausal women with a high stiffness index showed significantly improved vascular markers after MK-7 treatment, e.g., a decreased blood pressure at brachialis (−3.0% ± 9.0; p = 0.007) and an increased distensibility coefficient (+13.3% ± 32.3; p = 0.040). Conclusions: Our results confirm that menopause affects vascular health status. Post-menopausal women with an increased stiffness benefit most from MK-7 supplementation, with a significantly improved blood pressure. Further research is needed to unravel the beneficial effects of MK-7 in post-menopausal women. Full article

The aim of this study was to evaluate the potential effects of administering mangaba powder on liver function and somatic, oxidative and lipid metabolism parameters in rats fed a high-fat diet. Prepared mangaba powder has important amounts of phenolic compounds, vitamin C, dietary fiber and oligosaccharides. A total of 32 adult Wistar rats were initially randomized into two groups for the biological assay: normal-fat (NF, n = 16) and high-fat (HF, n = 16) diets for 21 days. These rats were subsequently subdivided into four groups: NF (n = 8), HF (n = 8), normal-fat diet with mangaba powder administration (NFMG, n = 8) and high-fat diet with mangaba powder administration (HFMG, n = 8). The treatment with mangaba powder (400 mg/kg) lasted an additional 28 days. Compared to the HF rats, the HFMG rats showed an 8% reduction in the body mass index. Treatment with mangaba reduced the serum cholesterol by 18%, as well as the hepatic deposition of triacylglycerides by 26% and cholesterol by 25%, in addition to increasing bile acid synthesis by 77% in this organ. Mangaba powder consumption attenuated the degree of hepatic steatosis, reduced lipid peroxidation and increased the serum and hepatic antioxidant capacity in HFMG rats. These results show that the consumption of mangaba powder had lipid-lowering, hepatoprotective and antioxidant effects, especially in HFMG rats, which may be associated with an additive and synergistic action between the bioactive compounds present in the product. Full article

Hyperlipidemia, characterized by an abnormal lipid metabolism, is related to multiple cardiovascular diseases that pose challenges to global public health. Macadamia oil (MO), rich in monounsaturated fatty acids (around 80%), is regarded as a functional oil used to regulate lipid accumulation. Nonetheless, the lipid-lowering mechanism of MO is still unknown. Therefore, the lipid-lowering effects of MO in high-fat diet (HFD)-induced hyperlipidemic mice were evaluated in this study. The results revealed that MO could effectively reduce body weight and the organ index and improve serum lipid levels by reducing total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels and elevating high-density lipoprotein cholesterol levels. Additionally, MO supplementation could improve abnormal liver function caused by hyperlipemia, characterized by decreased liver enzyme levels, including alanine aminotransferase and aspartate aminotransferase. Meanwhile, MO also exhibited an inhibitory effect on oxidative stress and lipid accumulation caused by an HFD. Moreover, findings from qRT-PCR and Western blotting analyses suggest that MO supplementation markedly prevented hyperlipidemia by inhibiting the expression of AMPK pathway-related genes, SREBP-1c, FAS, ACC, and PPAR-γ, as well as upregulating the levels of Nrf2, HO-1, and γ-GCS. These results indicate that MO attenuates lipid accumulation in vivo via AMPK/Nrf2 pathway activation, suggesting that MO could serve as a dietary supplementation or medication for treating hyperlipidemia. Full article