Assessment of aortomesenteric distance and mesenteric and retroperitoneal adipose tissue thickness in genetic forms of lipodystrophy.

INTRODUCTION: Lipodystrophy is a rare disease characterized by the loss of adipose tissue. Visceral adipose tissue loss in certain forms of lipodystrophy may affect the amount of mesenteric fat. METHOD: We studied visceral adipose tissue by measuring the thickness of mesenteric and retroperitoneal adipose tissue and the aortomesenteric (AOM) distance in patients with genetic forms of lipodystrophy (n = 48; 7 males; 41 females; mean age 39.1 ± 11.9 years; 19 with congenital generalized lipodystrophy [CGL], and 29 with familial partial lipodystrophy [FPLD]). An age- and gender-matched control group with a ratio of 1:2 was generated. RESULTS: Patients with CGL had severely depleted mesenteric adipose tissue (2.0 [IQR: 1.5-3.5] mm vs. 18.8 [IQR: 4.4-42.2] mm in FPLD, P < .001; 30.3 [IQR: 13.9-46.6] mm in controls, P < .001) and retroperitoneal adipose tissue (1.3 [IQR: 0.0-5.3] mm vs. 33.7 [IQR: 21.6-42.1] mm in FPLD, P < .001; 29.7 [IQR: 23.1-36.7] mm in controls, P < .001). The AOM distance was shorter in patients with CGL (8.1 [IQR: 6.0-10.8] mm) compared to patients with FPLD (vs. 13.0 [IQR: 8.8-18.1] mm; P = .023) and controls (vs. 11.3 [IQR: 8.4-15.5] mm, P = .016). Leptin levels were positively correlated with AOM distance in lipodystrophy (r = .513, P < .001). Multivariate linear regression analysis identified body mass index as a significant predictor of AOM distance (data controlled for age and sex; beta = 0.537, 95% CI: 0.277-0.798, P < .001). Twelve of 19 patients (63%) with CGL had an AOM distance of < 10 mm, a risk factor that may predispose patients to developing superior mesenteric artery syndrome. CONCLUSION: CGL is associated with a severe loss of mesenteric adipose tissue, which leads to a narrowing of the space between the superior mesenteric artery and the aorta.

Potential Mechanisms of Epicardial Adipose Tissue Influencing Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is the predominant terminal stage and the leading cause of mortality in cardiac disease. Heart failure with preserved ejection fraction (HFpEF) affects roughly 50% of HF patients globally. Due to the global aging population, the prevalence, morbidity, and mortality of HFpEF have gradually increased. Epicardial adipose tissue (EAT), as a key visceral adipose tissue around the heart, affects cardiac diastolic function and exercise reserve capacity. EAT closely adheres to the myocardium and can produce inflammatory factors, neurotransmitters, and other factors through autocrine or paracrine mechanisms, affecting the heart function by inflammatory response, cardiac metabolism and energy supply, cardiomyocyte structure and electrical activity, and pericardial vascular function. Currently, research on the mechanism and treatment methods of HFpEF is constantly improving. EAT may play a multi-level impact on the occurrence and development of HFpEF. This review also summarizes the potential impact of EAT on the heart in HFpEF combined with other metabolism-related diseases such as obesity or diabetes over other obesity-related measures, such as body mass index (BMI) or other adipose tissue. Above all, this review comprehensively summarizes the potential mechanisms by which EAT may affect HFpEF. The objective is to enhance our comprehension and management of HFpEF. Future research should delve into the mechanistic relationship between EAT and HFpEF, and investigate interventions aimed at EAT to improve the prognosis of patients with HFpEF.

A Prediction Nomogram of Severe Obstructive Sleep Apnea in Patients with Obesity Based on the Liver Stiffness and Abdominal Visceral Adipose Tissue Quantification.

Purpose: The diagnosis of severe OSA still relies on polysomnography, which causes a strong sense of restraint in patients with obesity. However, better prediction tools for severe OSA applicable to patients with obesity have not been developed. Patients and Methods: Relevant clinical data of 1008 patients with OSA who underwent bariatric surgery in our hospital were collected retrospectively. Patients were divided into training and test cohorts by machine learning. Univariate and multivariate logistic regression analysis was used to screen associations, including liver stiff measurement (LSM) and abdominal visceral tissue (aVAT), and to construct a severe OSA risk prediction nomogram. Then, we evaluated the effectiveness of our model and compared our model with the traditional Epworth Sleepiness Scale (ESS) model. Finally, our associations were used to explore the correlation with other indicators of OSA severity. Results: Our study revealed that age, biological sex, BMI, LSM, aVAT, and LDL were independent risk factors for severe OSA in patients with obesity. A severe OSA risk prediction nomogram constructed by six indicators possessed high AUC (0.845), accuracy (77.6%), and relatively balanced specificity and sensitivity (72.4%, 82.8%). The Hosmer-Lemeshow test (P=0.296, 0.785), calibration curves, and DCA of the training and test cohorts suggested better calibration and more net clinical benefit. Compared with the traditional ESS model, our model had higher AUC (0.829 vs 0.545), sensitivity (78.9% vs 12.2%), PPV (77.9% vs 53.3%), and accuracy (75.4% vs 55.2%). In addition, the associations in our model were independently correlated with other indicators reflecting OSA severity. Conclusion: We provided a simple, cheap, and non-invasive nomogram of severe OSA risk prediction for patients with obesity, which would be helpful for preventing further complications associated with severe OSA.

Question: Can we predict severe OSA in patients with obesity by their metabolic complications through some non-invasive examinations? Findings: Compared with traditional questionnaires, we developed and validated a new prediction model, including liver stiffness measurement and abdominal visceral adipose tissue, to screen severe OSA in bariatric surgery candidates through non-invasive examinations, which may contribute to perioperative safety and ultimate weight loss outcomes. Meaning: For patients with obesity who are in hospital because of metabolic disorders, it is necessary for them to be screened for possible severe OSA according to our new prediction nomogram, which is helpful for preventing further complications and perioperative risk associated with severe OSA.

Association between asthma and visceral adipose tissue in adults, a cross-sectional study from NHANES 2011-2018.

Asthma is a chronic inflammatory disease that affects millions of people worldwide. Obesity, particularly visceral adipose tissue (VAT), is known to secrete adipokines and pro-inflammatory factors, which are closely associated with various metabolic and cardiovascular diseases. Research indicates that these metabolic disturbances can exacerbate inflammatory conditions, contributing to both cardiovascular and respiratory diseases, including asthma. Despite these associations, studies on the specific relationship between VAT and asthma remain limited and warrant further investigation. Utilizing the NHANES database from 2011 to 2018, we included a total of 11,137 participants. Multivariable regression analysis was performed, stratifying subjects based on VAT levels and adjusting for various confounders. Subgroup interaction analysis and nonlinear analysis were conducted to explore potential effect modifiers and nonlinear associations. In this study, 11,137 participants were included, with 49.74% being female. Among the 509 asthma patients, 69.35% were female. The number of asthma patients among Non-Hispanic Whites was 212, representing 41.65% of the total, the highest proportion among the studied groups. The VAT for asthma patients was 529 g, significantly higher than the 455 g in the non-asthma group (P < 0.001). Multivariable regression analysis showed that for every 200 g increase in VAT, the risk of asthma increased by 10.4% (P = 0.032), 20.8% (P < 0.001), and 20.3% (P = 0.004) across three models (unadjusted, adjusted for demographic factors, and fully adjusted). Subgroup analysis indicated a stronger association between VAT and asthma risk in females and individuals over 40 years old. Nonlinear analysis uncovers a J-shaped relationship between VAT and asthma, with the lowest risk observed at 464.57 g (P < 0.001). The study findings suggest that increased VAT is associated with elevated asthma risk, particularly among females and older individuals. These results underscore the importance of considering VAT in asthma risk assessment and highlight potential targeted interventions to reduce asthma risk associated with excess visceral adiposity.

Causality of visceral adipose tissue on chronic kidney disease and renal function measure indicators, and mediation role of hypertension: Mendelian randomization study.

Although chronic kidney disease (CKD) is associated with obesity, few studies have used visceral adipose tissue (VAT) as an indicator to investigate its causal effect on CKD. Therefore, Mendelian randomization (MR) was employed to study the causal effects of VAT on CKD and its potential mediation by hypertension. Genome-wide association study (GWAS) statistics on VAT exposure were obtained from the UK Biobank, while GWAS datasets of CKD outcomes were obtained from CKDGen and FinnGen (validation study). Furthermore, VAT was considered the exposure, with the estimated glomerular filtration rate based on creatinine (eGFR (crea)), estimated glomerular filtration rate based on cystatin C (eGFR(cys)), and blood urea nitrogen (BUN) employed to assess the causal effect of VAT on kidney test indicators. Lastly, a two-step MR method was used to study the mediating role of hypertension in the pathogenesis of VAT among patients with CKD. VAT exhibited a positive causal association with CKD, irrespective of whether the GWAS datasets from CKDGen (odds ratio [OR] = 1.18, 95% CI: 1.08 to 1.29, P = 1.433140e-04) or FinnGen (1.47, 1.30 to 1.67, p = 2.500000e-09). VAT was not causally associated with eGFR (crea) (1.00, 0.99 to 1.00, p = 0.53), was negatively associated with eGFR (cys) (0.95, 0.93 to 0.97, P = 5.070000e-10), and was positively associated with BUN (1.02,1.01 to 1.02, P = 7.824860e-04). The mediating effect of VAT on CKD via hypertension was 45.8% (95% CI: 26.4 65.1). VAT has a positive causal effect on CKD, with hypertension playing a significant role. However, the effects of VAT on renal function indicators require further investigation.

Visceral adipose tissue for predicting severe acute pancreatitis.

Background & objectives Acute pancreatitis (AP) is a well known gastrointestinal cause of hospital admissions. There is a proven association between the severity of AP and obesity due to increased rates of local complications, multiple organ failure and mortality. Increased visceral adiposity is reported to be a better predictor of severe pancreatitis than body mass index (BMI) in many studies. This study aimed to assess the relationship between visceral adiposity and the severity of AP by measuring the visceral adipose tissue (VAT) area. Methods This single-centre, prospective study was conducted on consecutive individuals admitted with AP. The severity of AP was correlated with the VAT area, as estimated between 48 and 72 h of admission. Results Seventy-four individuals with AP were recruited during the study period. The overall study cohort's mean±SD for VAT area was 128.06±34.22 cm2. The VAT area was significantly larger in individuals with severe pancreatitis (141.01±33.75cm2) than in those with mild or moderate pancreatitis (115.11±29.85 cm2). The sensitivity, specificity and area under the receiver operating characteristics (AUROC) of VAT were 78.4 per cent, 54.1 per cent and 0.722 in predicting severe AP, respectively. Interpretation & conclusions There is a significant association between severe AP and VAT. With the worldwide increase in obesity incidences, incorporating VAT into one of the prognostic indices for AP needs to be further explored.

Preoperative Prediction of Her-2 and Ki-67 Status in Gastric Cancer Using 18F-FDG PET/CT Radiomics Features of Visceral Adipose Tissue.

Aims/Background Immunohistochemistry (IHC) is the main method to detect human epidermal growth factor receptor 2 (Her-2) and Ki-67 expression levels. However, IHC is invasive and cannot reflect their expression status in real-time. This study aimed to build radiomics models based on visceral adipose tissue (VAT)'s 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging, and to evaluate the relationship between radiomics features of VAT and positive expression of Her-2 and Ki-67 in gastric cancer (GC). Methods Ninety patients with GC were enrolled in this study. 18F-FDG PET/CT radiomics features were calculated using the PyRadiomics package. Two methods were employed to reduce radiomics features. The machine learning models, logistic regression (LR), and support vector machine (SVM), were constructed and estimated by the receiver operator characteristic (ROC) curve. The correlation of outstanding features with Ki-67 and Her-2 expression status was evaluated. Results For the Ki-67 set, the area under of the receiver operator characteristic curve (AUC) and accuracy were 0.86 and 0.79 for the LR model and 0.83 and 0.69 for the SVM model. For the Her-2 set, the AUC and accuracy were 0.84 and 0.86 for the LR model and 0.65 and 0.85 for the SVM model. The LR model for Ki-67 exhibited outstanding prediction performance. Three wavelet transform features were correlated with Her-2 expression status (p all < 0.001), and one wavelet transform feature was correlated with the expression status of Ki-67 (p = 0.042). Conclusion 18F-FDG PET/CT-based radiomics models of VAT demonstrate good performance in predicting Her-2 and Ki-67 expression status in patients with GC. Radiomics features can be used as imaging biomarkers for GC.

Accelerated BDNF expression in visceral white adipose tissues following high-fat diet feeding in mice.

Brain-derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high-fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia-inducible factor 1α (Hif1α) and platelet-derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti-inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues.

Visceral and subcutaneous adiposity and cardiovascular disease: Unravelling associations and prognostic value.

AIM: The distribution pattern of abdominal adiposity may help determine cardiovascular disease (CVD). Waist circumference (WC) is the most common but imprecise method for measuring abdominal adiposity, as it fails to differentiate between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT). This study aimed to determine whether elevated VAT or ASAT provides greater prognostic value for CVD events compared to elevated WC in the general population using data from the UK Biobank. MATERIALS AND METHODS: In this secondary analysis of UK Biobank study, 24 265 participants with available abdominal magnetic resonance imaging data were included. The primary outcome of the study was coronary heart disease (CHD), and secondary outcomes included stroke, heart failure (HF) and atrial fibrillation (AF). Cox regressions for VAT, ASAT and WC were examined in relation to the predefined outcomes on continuous scales using standard deviation (SD) changes and by categories of concordant and discordant values defined by medians. RESULTS: During a mean follow-up period of 12.9 ± 1.8 years, 2641 participants developed CVD events (1296 CHD, 165 stroke, 286 HF and 894 AF) Each 1 SD increase in VAT yielded a hazard ratio (HR) of 1.15 (95% confidence interval [CI]: 1.09-1.22) for CHD risk, whereas ASAT had a HR of 1.10 (95% CI: 1.04-1.18). Further adjustment for WC eliminated the association between ASAT and CHD risk, in contrast to the association between VAT and CHD risk, which remained almost unaffected. Discordant VAT above the median with WC below presented a HR of 1.43 (95% CI: 1.15-1.78) for CHD, compared with concordant VAT and WC below the median. Similar results were found for discordant WC above the median with VAT below, with a HR of 1.46 (95% CI: 1.18-1.81). In contrast, discordant ASAT above the median with WC below was not associated with an increased risk of CHD. Similarly, discordant ASAT above the median with VAT below was not associated with an increased risk of CHD. Additionally, there was no observed association between VAT or ASAT and the risks of stroke, HF or AF after further adjustment for WC. Additionally, there was no observed association between VAT or ASAT and the risks of stroke, HF or AF after further adjustment for WC. CONCLUSION: Incorporating VAT measurements alongside WC data improved the ability to identify individuals at high risk for CHD compared to using WC alone. Both VAT and WC proved to be more accurate indicators of CHD risk than ASAT. However, VAT alone did not fully account for the CHD risk associated with elevated WC levels. Neither VAT nor ASAT showed an association with the risk of stroke, HF and AF.

Message Transmission Between Adipocyte and Macrophage in Obesity.

Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction have primary importance in obesity. Large quantity of macrophages is accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway promotes more macrophage accumulation into the obese adipose tissue. However, obesity-induced changes in adipose tissue macrophage density are mainly dependent on increases in the triple-positive cluster of differentiation (CD)11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. As epigenetic regulators, microRNAs (miRNAs) are one of the most important mediators of obesity. miRNAs are expressed by adipocytes as well as macrophages and regulate inflammation with the expression of target genes. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-α) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1ß) by macrophages; both adipocyte and macrophage induction by toll-like receptor-4 (TLR4) through nuclear factor-kappaB (NF-κB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in mutual message transmission between adipocyte and macrophage and in the development of adipose tissue inflammation. Thus, the metabolic status of adipocytes and their released exosomes are important determinants of macrophage inflammatory output. However, old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. As a single miRNA can be able to regulate a variety of target genes and signaling pathways, reciprocal transfer of miRNAs between adipocytes and macrophages via miRNA-loaded exosomes reorganizes the different stages of obesity. Changes in the expression of circulating miRNAs because of obesity progression or anti-obesity treatment indicate that miRNAs could be used as potential biomarkers. Therefore, it is believed that targeting macrophage-associated miRNAs with anti-obesity miRNA-loaded nano-carriers may be successful in the attenuation of both obesity and adipose tissue inflammation in clinical practice. Moreover, miRNA-containing exosomes and transferable mitochondria between the adipocyte and macrophage are investigated as new therapeutic targets for obesity-related metabolic disorders.

Computed tomography-based intermuscular adipose tissue analysis and its predicting role in post-kidney transplantation diabetes mellitus.

BACKGROUND: While body mass index (BMI) is the most widely used indicator as a measure of obesity factors in post-transplantation diabetes mellitus (PTDM), body composition is a more accurate measure of obesity. This study aims to investigate the effects of Computed tomography (CT)--based morphemic factors on PTDM and establish a prediction model for PTDM after kidney transplantation. METHODS: The pre-transplant data and glycemic levels of kidney transplant recipients (June 2021 to July 2023) were retrospectively and prospectively collected. Univariate and multivariate analyses were conducted to analyze the relationship between morphemic factors and PTDM at one month, six months, and one year after hospital discharge. Subsequently, a one-year risk prediction model based on morphemic factors was developed. RESULTS: The study consisted of 131 participants in the one-month group, where Hemoglobin A1c (HbA1c) (p = 0.02) was identified as the risk factor for PTDM. In the six-month group, 129 participants were included, and the intermuscular adipose tissue (IMAT) area (p = 0.02) was identified as the risk factor for PTDM. The one-year group had 128 participants, and the risk factors for PTDM were identified as body mass index (BMI) (p = 0.02), HbA1c (p = 0.01), and IMAT area (p = 0.007). HbA1c (%) and IMAT area were included in the risk prediction Model for PTDM in the one-year group with AUC = 0.716 (95 % CI 0.591-0.841, p = 0.001). CONCLUSIONS: Compared to BMI and other morphemic factors, this study demonstrated that the IMAT area was the most potential predictor of PTDM. CLINICAL TRIAL NOTATION: Chictr.org (ChiCTR2300078639).

Abdominal visceral-to-subcutaneous fat ratio in the prediction of metabolic syndrome risk in Japanese Americans followed prospectively for 10-years loses information.

AIMS: Visceral fat predicts the development of metabolic syndrome (MetS), but it is not known whether the visceral to subcutaneous fat area ratio (VSR) measured using imaging predicts MetS risk as well or better. Thus, we aimed to examine if VSR predicted future risk of MetS over 10-years. METHODS: We followed 329 participants in the longitudinal Japanese American Community Diabetes Study without MetS at baseline for its development over 10 years. Intra-abdominal (VFA) and subcutaneous abdominal (SFA) fat areas were measured at baseline and 10-years and used to calculate VSR. Logistic regression was used to estimate the odds of incident MetS by baseline and 10-year change in VSR and other adipose depots with and without adjustment for baseline MetS features. Areas under ROC curves were calculated in predicting the development of MetS. RESULTS: 99 participants developed MetS over 10-years. Logistic regression models showed a higher odds of incident MetS with greater VSR and 10-year VSR change (OR = 1.67, 95 % CI 1.11-2.51; OR = 1.46, 95 % CI 1.06-2.01, respectively) adjusting for age, sex, and MetS features at baseline. However, VSR alone performed poorly at discriminating (AUROC 0.5807) compared to VFA (AUROC 0.6970, p < 0.001) or a logistic model incorporating VFA and SFA (AUROC 0.7221, p = 0.001). CONCLUSIONS: VSR and VFA predict 10-year MetS risk in Japanese Americans, confirming the importance of relatively greater fat distribution in the visceral depot in the development of MetS. However, VSR is a weaker predictor of MetS development and provides less information compared to VFA alone, and its further use in predicting metabolic abnormalities is not recommended.

Interleukin-27 signaling resists obesity by promoting the accumulation of Treg cells in visceral adipose tissue.

The prevalence of obesity and its associated metabolic disorders has emerged as one of the most significant health threats worldwide. The visceral adipose tissue regulatory T cells (VAT Treg) play an essential role in maintaining homeostasis and preventing obesity mainly by secreting Interleikin-10 (IL-10) and Transforming Growth Factor ß (TGF-ß). However, the mechanism that regulates VAT Treg quantity and function remains unclear. Here we elucidate the pivotal role of IL-27 signaling in sustaining the accumulation of VAT Treg cells, thereby conferring protection against obesity. We found that mice with the deficiency of IL-27 receptor Wsx1 gained more body weight and VAT weight than their wild-type littermates when fed both a normal-fat diet (NFD) and a high-fat diet (HFD). Notably, the population of VAT Treg cells was reduced in Wsx1 knockout (KO) mice, regardless of whether they were fed a normal-fat diet (NFD) or a high-fat diet (HFD). Correspondingly, the expression levels of the transcription factors FOXP3 and PPAR-γ, essential for VAT Treg function, were also diminished in Wsx1 KO mice. Taken together, our findings indicate that IL-27 signaling plays a protective role in obesity by supporting the maintenance and accumulation of VAT Treg cells.

The association between visceral adipose accumulation and hyperuricemia risk among Chinese elder individuals: A nationwide prospective cohort study.

Background: Lipid accumulation product (LAP), visceral adiposity index (VAI) and Chinese visceral adiposity index (CVAI) are proposed indices of visceral adipose accumulation. This study aimed to explore their relationship and temporal changes with hyperuricemia (HUA) development in a Chinese population. Methods: A total of 4268 participants aged ≥45 years from the baseline survey of the China Health and Retirement Longitudinal Study were followed up for 4 years (from 2011 to 2015). The relationships among VAI, LAP, CVAI and HUA were analyzed using logistic regression. The predictive abilities of the VAI, LAP and CVAI for HUA were compared using receiver operating characteristic curves. Nonlinear relationships between the indices and HUA were analyzed using restricted cubic spline regression. Results: During the four-year follow-up, 415 (9.72 %) patients experienced incident HUA . Elevated baseline VAI (odds ratio (OR): 1.19 (95 % confidence interval (95 %CI: 1.10, 1.29)), LAP (OR: 1.21 (95 % CI: 1.09, 1.34)) and CVAI (OR: 1.19 (95 % CI: 1.02, 1.40)) were significantly correlated with increased HUA risk (all P < 0.05). Compared to individuals with consistently low VAI,CVAIor LAP levels, those with elevated or consistently high levels of these indicators are more likely to have HUA. The area under curve (AUC) was slightly greater and more significant for the CVAI (AUC=0.641) than for the VAI (AUC=0.604) and LAP (AUC=0.628) (P < 0.05). Conclusion: VAI, LAP and CVAI can predict HUA, with CVAI more efficient than VAI and LAP. Early management can lessen the burden of HUA in Chinese people aged 45 years or older with elevated CVAI levels.

Epigenetic profiles in blood and adipose tissue: identifying strong correlations in morbidly obese and non-obese patients.

Epigenetic alterations play a pivotal role in conditions influenced by environmental factors such as overweight and obesity. Many of these changes are tissue-specific, which entails a problem in its study since obtaining human tissue is a complex and invasive practice. While blood is widely used as a surrogate biomarker, it cannot directly extrapolate the evidence found in blood to tissue. Moreover, the intricacies of metabolic diseases add a new layer of complexity, as obesity leads to significant alterations in adipose tissue, potentially causing associated pathologies that can disrupt existing correlations seen in healthy individuals. Here, our objective was to determine which epigenetic markers exhibit correlations between blood and adipose tissue, regardless of the metabolic status. We collected paired blood and adipose tissue samples from 64 patients with morbidity obesity and non-obese and employed the MethylationEPIC 850 K array for analysis. We found that only a small fraction, specifically 4.3% (corresponding to 34,825 CpG sites), of the sites showed statistically significant correlations (R ≥ 0.6) between blood and adipose tissue. Within this subset, 5327 CpG sites exhibited a strong correlation (R ≥ 0.8) between blood and adipose tissue. Our findings suggest that the majority of epigenetic markers in peripheral blood do not reliably reflect changes occurring in visceral adipose tissues. However, it is important to note that there exists a distinct set of epigenetic markers that can indeed mirror changes in adipose tissue within blood samples. KEY MESSAGES: More than 8% of methylation sites exhibit similarity between blood and adipose tissues, regardless of BMI The correlation percentage between blood and adipose tissue is strongly influenced by gender The principal genes implicated in this correlation are related to metabolism or the immunological system.

A long-term high fat diet induces differential gene expression changes in spatially distinct adipose tissue of male mice.

The accumulation of visceral adipose tissue (VAT) is strongly associated with cardiovascular disease and diabetes. In contrast, individuals with increased subcutaneous adipose tissue (SAT) without corresponding increases in VAT are associated with a metabolic healthy obese phenotype. These observations implicate dysfunctional VAT as a driver of disease processes, warranting investigation into obesity-induced alterations of distinct adipose depots. To determine the effects of obesity on adipose gene expression, male mice (n=4) were fed a high fat diet to induce obesity or a normal laboratory diet (lean controls) for 12-14 months. Mesenteric VAT and inguinal SAT were isolated for bulk RNA-sequencing. AT from lean controls served as a reference to obesity-induced changes. The long-term high fat diet induced the expression of 169 and 814 unique genes in SAT and VAT, respectively. SAT from obese mice exhibited 308 differentially expressed genes (164 upregulated, 144 downregulated). VAT from obese mice exhibited 690 differentially expressed genes (262 genes upregulated, 428 downregulated). KEGG pathway and GO analyses revealed that metabolic pathways were upregulated in SAT vs. downregulated in VAT while inflammatory signaling was upregulated in VAT. We next determined common genes that were differentially regulated between SAT and VAT in response to obesity and identified four genes that exhibited this profile: elovl6 and kcnj15 were upregulated in SAT/downregulated in VAT while trdn and hspb7 were downregulated in SAT/ upregulated in VAT. We propose that these genes in particular should be further pursued to determine their roles in SAT vs. VAT with respect to obesity.

Liver transplant recipients have worse metabolic body phenotype compared with matched non-transplant controls.

Background and Aim: Quantification of body compartments, particularly the interaction between adipose tissue and skeletal muscle, is emerging as novel a biomarker of metabolic health. The present study evaluated the impact of liver transplant (LT) on body compartments. Methods: Totally 66 adult LT recipients were enrolled in whom body compartments including visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), muscle fat infiltration (MFI), fat-free muscle volume (FFMV), and liver fat (LF) were quantified via whole body magnetic resonance imaging (MRI). To provide non-LT comparison, each LT recipient was matched to at least 150 non-LT controls for same sex, age, and body mass index (BMI) from the UK Biobank registry. Results: LT recipients (vs matched non-LT controls) had significantly higher subcutaneous (13.82 ± 5.47 vs 12.10 ± 5.10 L, P < 0.001) and visceral fat (7.59 ± 3.75 vs 6.72 ± 3.06 L, P = 0.003) and lower LF (5.88 ± 7.14 vs 8.75 ± 6.50%, P < 0.001) and muscle volume (11.69 ± 2.95 vs 12.12 ± 2.90 L, P = 0.027). In subgroup analysis, patients transplanted for metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis (vs non-MASH cirrhosis) had higher ASAT, VAT, and MFI. A trend toward higher LF content was noted; however, this did not reach statistical significance (6.90 ± 7.35 vs 4.04 ± 6.23%, P = 0.189). Finally, compared with matched non-LT controls, patients transplanted for MASH cirrhosis had higher ASAT and VAT; however, FFMV and MFI were similar. Conclusion: Using non-LT controls, the current study established the higher-than-expected adiposity burden among LT recipients, which is even higher among patients transplanted for MASH cirrhosis. These findings provide data needed to design future studies developing radiomics-based risk-stratification strategies in LT recipients.

Impact of BMI and Body Composition on First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear. PATIENTS AND METHODS: In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m2) and low- (<25 kg/m2) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated. RESULTS: Patients with a high BMI had lower skeletal mass index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) compared to those in the low-BMI cohort. The baseline Child-Pugh scores and Barcelona Clinic Liver Cancer stages were comparable between the two cohorts. The overall survival (OS) was better in the high BMI group compared to the low BMI group (median, 913 vs. 484 days; p=0.008). SMI had a strong influence on OS. Additionally, low BMI, VATI, SATI, and visceral-to-subcutaneous fat ratio (VSR) in the LEN treatment group were associated with shorter progression-free survival (PFS). CONCLUSION: Following systemic treatment for uHCC, patients with low BMI have a poor prognosis. Among anthropometric factors, low SMI is associated with poor OS. In the LEN treatment group, low VATI may impact PFS negatively.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as "unhealthy macrophages". Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Effect of contrast phase on quantitative analysis of skeletal muscle and adipose tissue by computed tomography.

OBJECTIVES: Significant variability exists in the contrast phases applied during computed tomography (CT) studies when assessing morphometric measurements of muscle area (CT-assessed sarcopenia) and density (CT-assessed myosteatosis) and visceral adipose tissue area (CT-assessed visceral obesity). This study explored the impact of contrast phase timing on changes in morphometric measurements of body composition. METHODS: This single-center retrospective cohort study included 459 patients undergoing a multiphase CT scan. Morphometric measurements were obtained at the third lumbar vertebra level. Patients were classified as sarcopenic, myosteatotic, or visceral obese using predefined cutoff values. The intraclass correlation coefficient was used to assess correlations across different enhancement phases, and Cohen's κ measured the inter-enhancement agreement for sarcopenia, myosteatosis, and visceral obesity. RESULTS: Significant differences were observed in mean visceral adipose tissue area, muscle density, and muscle area (P < 0.001). The intraclass correlation coefficient between unenhanced and arterial phases was 0.987 (95% confidence interval [CI], 0.759-0.996) for adipose tissue, 0.995 (95% CI, 0.989-0.997) for muscle area, and 0.850 (95% CI, 0.000-0.956) for muscle density. However, when morphometric measurements were categorized using predefined cutoffs, the κ agreement was considerably lower, particularly for CT-assessed myosteatosis, ranging from 0.635 (unenhanced to arterial) to 0.331 (unenhanced to late venous phase). CONCLUSIONS: Different CT contrast phases induce small but clinically significant alterations in the measurements of muscle area and density and visceral fat. Such minor changes can result in misclassification issues when fixed cutoff values are used to diagnose myosteatosis with CT. This underscores the importance of reporting absolute values and the specific contrast phase used in future studies.