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Background: Obesity is a major contributing factor to the formation of gallstones. As early identification typically results in improved outcomes, we explored the relationship between visceral lipid accumulation indicators and the occurrence of gallstones., Methods: This cross-sectional study involved 3,224 adults. The researchers employed multivariable logistic regression, smoothed curve fitting (SCF), threshold effects analysis, and subgroup analysis to examine the relationship between metabolic scores for visceral fat (METS-VF), waist circumference (WC), lipid accumulation products (LAP), and visceral adiposity index (VAI) and gallstones. A Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to identify key factors which were then used in the construction of a nomogram model. The diagnostic efficacy of this model in detecting gallstones was then determined using receiver operating characteristic curves., Results: Visceral lipid accumulation indicators were strongly linked to the likelihood of having gallstones. Specific saturation effects for METS-VF, WC, LAP, and VAI and gallstones were determined using SCF. The inflection points for these effects were found to be 8.565, 108.400, 18.056, and 1.071, respectively. Subgroup analyses showed that associations remained consistent in most subgroups. The nomogram model, which was developed using critical features identified by LASSO regression, demonstrated excellent discriminatory ability, as indicated by an area under the curve value of 0.725., Conclusions: Studies have shown that increases in METS-VF, WC, LAP, and VAI are linked to increased prevalences of gallstones. The nomogram model, designed with critical parameters identified using LASSO regression, exhibits a strong association with the presence of gallstones., (© 2024. The Author(s).)

Aims/introduction: To investigate whether sarcopenic obesity is associated with the progression of atherosclerotic lesions in older patients with diabetes and to identify the obesity components of sarcopenic obesity that best reflect atherosclerosis., Materials and Methods: In 118 inpatients aged ≥75 years with diabetes mellitus, sarcopenia defined as a low skeletal muscle mass and low grip strength was assessed, and sarcopenia coexisting with a high body-fat percentage or visceral fat area was defined as sarcopenic obesity. Correlations between the obesity components and atherosclerotic markers, including the carotid intima-media thickness, were analyzed; the intima-media thickness was analyzed in four groups with and without obesity and sarcopenia, and a multiple linear regression analysis adjusted for covariates was conducted to investigate whether sarcopenic obesity was independently associated with the intima-media thickness., Results: The visceral fat area and intima-media thickness showed positive correlations in the overall patients (P = 0.032) and the sarcopenia (P = 0.016) group but showed no associations in participants without sarcopenia. The intima-media thickness in the group showing sarcopenia with a high visceral fat area was significantly higher than that in the control group (P = 0.012). Sarcopenic obesity defined by a high body-fat percentage and high visceral fat area was independently associated with the intima-media thickness even after adjusting for age, sex, and atherogenic risk factors. However, sarcopenic obesity defined by a high visceral fat area was more strongly associated with the intima-media thickness (β = 0.384, P = 0.002) than that defined by the high body-fat percentage (β = 0.237, P = 0.068)., Conclusions: Sarcopenic obesity, especially that defined by visceral fat accumulation, reflected the risk of atherosclerotic lesion progression in older patients with diabetes., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Obesity stands as an essential factor contributing to infertility in women. Early identification of obese individuals leads to favorable results for female infertility. The objective of this research is to assess the association between the age-adjusted visceral adiposity index (AVAI) and female infertility., Methods: This study was conducted using NHANES data from 2013 to 2018, in which 1,231 women aged 20-45 were selected. Infertility was defined by survey questions. AVAI was calculated using anthropometric and serum data. Covariates included demographics and lifestyle factors. Statistical analysis with R, adjusting for covariates, and assessing nonlinearity and cutoff effects., Results: The study of 1,231 women from the NHANES database revealed that 11.94% were diagnosed with infertility. Individuals with higher AVAI scores showed increased age, WC, BMI, and reduced HDL levels, with a positive correlation between AVAI and female infertility (OR = 1.42, 95%CI: 1.26-1.60). AVAI quartiles showed a pronounced relationship with female infertility risk, with the highest quartile showing the greatest risk(OR = 9.35,95% CI: 2.96-29.55). Nonlinear and threshold effects in the relationship between AVAI and female infertility were identified, with an inflection point at -9.70. Subgroup analyses indicated significant interactions between AVAI and educational status and BMI, particularly in women with a BMI below 25 kg/m 2 , where a high AVAI level was closely related to increased infertility risk(OR = 1.92, 95%CI: 1.44-2.58)., Conclusion: The study identifies a strong association between elevated AVAI scores and female infertility risk, especially in women with a BMI under 25 kg/m 2 . This suggests that AVAI could be a valuable predictor in female fertility assessments., (© 2024. The Author(s).)

Background: The distribution of body fat and metabolic health may contribute to the onset of metabolic syndrome (MetS), but the associations between body fat anthropometric indices (AIs) and mortality in individuals with MetS remain unclear., Methods: Participants aged 18 years or older with MetS were recruited from the NHANES 1999-2018. The body fat anthropometric indices included the a body shape index (ABSI), body roundness index (BRI), cardiometabolic index (CMI), visceral adiposity index (VAI), waist triglyceride index (WTI), lipid accumulation product (LAP), atherogenic index of plasma (AIP), and triglyceride‒glucose (TyG) index. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. Mortality data were obtained from the National Death Index through December 31, 2019., Results: Data were collected from 8,379 individuals with MetS, with a median follow-up of 8.5 years, of whom 1,698 died from all causes and 568 from the CCD. The random survival forest (RSF) analysis indicated that the ABSI had the strongest predictive power for both all-cause mortality and CCD mortality among the eight body fat AIs. After adjusting for multiple variables, the ABSI was found to be linearly and positively associated with all-cause and CCD mortality in individuals with MetS. Participants in the highest quartile of ABSI had an increased risk of all-cause (HR = 1.773 [1.419-2.215]) and CCD (HR = 1.735 [1.267-2.375]) mortality compared with those in the lowest quartile. Furthermore, the ABSI predicted areas under the curve (AUCs) of 0.735, 0.723, 0.718, and 0.725 for all-cause mortality at 3, 5, 10, and 15 years, respectively, and 0.774, 0.758, 0.725, and 0.715 for CCD mortality, respectively., Conclusion: Among eight body fat AIs, the ABSI exhibited the strongest predictive power for mortality in individuals with MetS. Higher ABSI values significantly increased all-cause mortality and CCD mortality in participants with MetS., (© 2024. The Author(s).)

Background: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes., Methods: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests., Results: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX., Conclusion: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis., (© 2024. The Author(s).)

Recent reports have shown that pre-treatment low muscle mass may lead to poorer outcomes for cancer patients. We explored the correlation between Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT), and Muscle Mass (MM) as measured by CT scans, and overall survival (OS) following diagnosis of colorectal cancer (CRC). We conducted a retrospective review of medical records and CT scans of patients diagnosed with CRC between 2007 and 2018. Demographics, pathology, and clinical parameters were collected. Using Image-J software, we measured VAT, SAT, and MM. Survival rates were analyzed using Kaplan-Meier curves, and prognostic factors were assessed using multivariate Cox regression. Analysis included 408 patients with a mean age of 56.9 years and a median follow-up of 93.3 months. Colon and rectum/rectosigmoid colon cancers were equally distributed. The 5-year OS rate was 67.8%. There was no significant difference in OS rates based on SAT or VAT. However, higher MM was associated with a improved 5-year OS rate. Factors such as age, stage, grade, and surgery were also associated to OS rates. These findings suggest that higher muscle mass may lead to better outcomes for CRC patients, highlighting the potential impact of exercise and nutritional interventions on patient outcomes., (© 2024. The Author(s).)

Background: Heterogenous deposition and homeostasis roles of physiologic and ectopic adipose tissues underscore the impact of fat compartmentalization on cardiometabolic risk. We aimed to characterize the distribution of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and liver fat on magnetic resonance imaging (MRI), and evaluate their associations with anthropometric indices and adverse cardiac remodeling., Methods: In this cross-sectional observational study, 149 Asian adults (57.0 ± 12.8 years; 65% males) with at least one cardiometabolic risk factor underwent multiparametric fat and cardiovascular MRI. Anthropometric indices included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and bioimpedance body fat mass (BFM). Associations between fat depots and anthropometric measures as well as cardiac remodeling features were examined as a single cohort and stratified by type 2 diabetes mellitus (T2DM) status., Results: VAT and SAT had opposing associations with liver fat and EAT. Therefore the VAT/SAT ratio was explored as an integrated marker of visceral adiposity. VAT/SAT was positively associated with EAT (β=0.35, P<0.001) and liver fat (β=0.32, P=0.003) independent of confounders. Of the anthropometric measurements assessed, only WHR was independently associated with VAT/SAT (β=0.17, P=0.021). Individuals with T2DM had higher VAT and lower SAT compared to those without T2DM, translating to a significantly higher VAT/SAT ratio. EAT volume was independently associated with adverse features of cardiac remodeling: increased left ventricular (LV) mass (β=0.24, P=0.005), larger myocyte volume (β=0.26, P=0.001), increased myocardial fibrosis (β=0.19, P=0.023), higher concentricity (β=0.18, P=0.035), and elevated wall stress (β=-0.18, P=0.023)., Conclusion: Multiparametric MRI revealed abdominal VAT and SAT have differential associations with anthropometric indices and ectopic fats in a single cohort of Asians at risk of cardiometabolic disease. People with T2DM have expanded VAT and diminished SAT, endorsing the VAT/SAT ratio beyond usual anthropometric measurements as a marker for multiorgan visceral fat composition. Among the fat depots examined, EAT is uniquely associated with adverse cardiac remodeling, suggesting its distinctive cardiometabolic properties and implications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Han, Toh, Bryant, Boubertakh, Le and Chin.)

Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.

Background: Based on the JCOG1109 trial, it is suggested that the combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) could potentially become a standard neoadjuvant chemotherapy regimen, alongside the conventional 5-fluorouracil and cisplatin (CF) therapy, for esophageal cancer. However, there are few reports on the impact of body composition changes associated with neoadjuvant chemotherapy on prognosis., Aim: Our study aimed to explore the effect of different neoadjuvant chemotherapy regimens on body composition during treatment and the impacts of body composition changes on their prognosis., Methods and Results: This is a retrospective study of 215 patients with advanced thoracic esophageal cancer who had surgery after neoadjuvant chemotherapy from 2013 to 2019. Computed tomography scans were performed before and after neoadjuvant chemotherapy to assess body composition. Skeletal muscle mass index (SMI) was calculated by dividing total skeletal muscle mass at the 3rd lumbar level by the square of height, while visceral and subcutaneous fat masses were measured at the level of umbilicus. Patients in the lowest 25% of both sexes were classified into the low visceral fat and low subcutaneous fat groups, respectively. Of the patients enrolled, 178 were male and 37 were female. Among them, 91 had clinical Stage II disease, and 124 had clinical Stage III disease. Additionally, 146 patients received neoadjuvant chemotherapy CF, and 69 received neoadjuvant chemotherapy DCF. Comparing the DCF and CF groups, the DCF group consisted of significantly younger patients (p < .01), a higher proportion of males (p = .03), and a greater number of clinical Stage III cases (p < .01). However, although percent change in SMI and visceral fat mass was not significantly different between two regimens, percent change in subcutaneous fat mass was significant in the DCF group. The major prognostic factors for patients undergoing surgery after neoadjuvant chemotherapy for thoracic esophageal cancer were clinical Stage III, transition to low visceral fat, and response rating (SD/PD), while the specific neoadjuvant chemotherapy regimen did not significantly influence the outcomes., Conclusion: This study suggests that prevention of the shift to low visceral fat throughout the neoadjuvant chemotherapy process should improve patient outcomes., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Objective: Perirenal adipose tissue (PAT) has emerged as a potential therapeutic target for cardiovascular disease (CVD). However, the relationship between increased perirenal fat thickness (PrFT) and CVD risks in individuals with type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to evaluate the association between PrFT and the estimated 10-year risk of CVD and atherosclerotic cardiovascular disease (ASCVD) in T2DM., Method: The final analysis included 704 participants. PrFT was quantified using non-enhanced computed tomography scans, while the estimated 10-year CVD and ASCVD risk assessments were based on the Framingham and China-PAR equation risk scores, respectively. Multiple regression analysis was employed to analyze the correlation between PrFT and these risk scores., Results: Higher quartiles of PrFT displayed elevated Framingham and China-PAR equation risk scores ( P <0.001). After adjusting for cardiometabolic risk factors and visceral fat area, PrFT remained significantly correlated with Framingham equation risk scores in men ( β =0.098, P =0.036) and women ( β =0.099, P =0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men ( β =0.106, P =0.009) and women ( β =0.108, P =0.007). Moreover, PrFT emerged as an independent variable associated with a high estimated 10-year risk of CVD and ASCVD, with odds ratios (ORs) of 1.14 (95% CI: 1.04-1.25, P =0.016) in men and 1.20 (95% CI: 1.11-1.31, P <0.001) in women for high estimated CVD risk, and ORs of 1.22 (95% CI: 1.08-1.41, P =0.009) in men and 1.34 (95% CI: 1.12-1.60, P <0.001) in women for high estimated 10-year ASCVD risk. Furthermore, restricted cubic spline analyses confirmed a nonlinear relationship between PrFT and high estimated CVD and ASCVD risk in both genders ( P for nonlinearity and overall < 0.05)., Conclusions: PrFT contributed as an independent variable to the estimated 10-year risk of CVD and ASCVD in T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Lv, Tu and Guo.)

Objectives: Accurate preoperative prediction of the pathological grade of clear cell renal cell carcinoma (ccRCC) is crucial for optimal treatment planning and patient outcomes. This study aims to develop and validate a deep-learning (DL) algorithm to automatically segment renal tumours, kidneys, and perirenal adipose tissue (PRAT) from computed tomography (CT) images and extract radiomics features to predict the pathological grade of ccRCC., Methods: In this cross-ethnic retrospective study, a total of 614 patients were divided into a training set (383 patients from the local hospital), an internal validation set (88 patients from the local hospital), and an external validation set (143 patients from the public dataset). A two-dimensional TransUNet-based DL model combined with the train-while-annotation method was trained for automatic volumetric segmentation of renal tumours, kidneys, and visceral adipose tissue (VAT) on images from two groups of datasets. PRAT was extracted using a dilation algorithm by calculating voxels of VAT surrounding the kidneys. Radiomics features were subsequently extracted from three regions of interest of CT images, adopting multiple filtering strategies. The least absolute shrinkage and selection operator (LASSO) regression was used for feature selection, and the support vector machine (SVM) for developing the pathological grading model. Ensemble learning was used for imbalanced data classification. Performance evaluation included the Dice coefficient for segmentation and metrics such as accuracy and area under curve (AUC) for classification. The WHO/International Society of Urological Pathology (ISUP) grading models were finally interpreted and visualized using the SHapley Additive exPlanations (SHAP) method., Results: For automatic segmentation, the mean Dice coefficient achieved 0.836 for renal tumours and 0.967 for VAT on the internal validation dataset. For WHO/ISUP grading, a model built with features of PRAT achieved a moderate AUC of 0.711 (95% CI, 0.604-0.802) in the internal validation set, coupled with a sensitivity of 0.400 and a specificity of 0.781. While model built with combination features of the renal tumour, kidney, and PRAT showed an AUC of 0.814 (95% CI, 0.717-0.889) in the internal validation set, with a sensitivity of 0.800 and a specificity of 0.753, significantly higher than the model built with features solely from tumour lesion (0.760; 95% CI, 0.657-0.845), with a sensitivity of 0.533 and a specificity of 0.767., Conclusion: Automated segmentation of kidneys and visceral adipose tissue (VAT) through TransUNet combined with a conventional image morphology processing algorithm offers a standardized approach to extract PRAT with high reproducibility. The radiomics features of PRAT and tumour lesions, along with machine learning, accurately predict the pathological grade of ccRCC and reveal the incremental significance of PRAT in this prediction., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased , glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by a carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PD S188F ) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PD S188F variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PD S188F variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PD S188F variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Previous studies have shown that sarcopenic obesity (SO) was associated with nonalcoholic fatty liver disease (NAFLD). However, research is limited in the context of the NAFLD renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) defined by updated diagnostic criteria. The aim of this study was to use the index skeletal muscle mass to visceral fat area ratio (SVR) to describe SO in a large and representative US population (National Health and Nutrition Examination Survey 2017-2018) of adults and investigate their association with MASLD., Methods: A total of 2087 individuals were included in the analysis. SVR was calculated according to the measurement of dual-energy x-ray absorptiometry and MASLD was diagnosed with controlled attenuation parameter scores and cardiometabolic risk factors. SVR was divided into tertiles. Logistic regression adjusted for confounders was used to evaluate the association between SVR and MASLD. Several sensitivity analyses were performed to test the robustness of our findings., Results: In a multivariate logistic regression analysis, a significant association between SVR and MASLD was shown (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 1.31-7.39, p = .010 for middle levels of SVR; OR: 3.82, 95% CI: 1.45-10.08, p = .007 for lowest levels of SVR). The sensitivity analyses confirmed that the association was robust., Conclusion: Our findings imply that decreased SVR is linked to MASLD., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes. Here, we demonstrate that obese AT microenvironment triggers the release of miR-210-3p microRNA-loaded extracellular vesicles from adipose tissue macrophages, which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity. Moreover, EVs collected from Dicer-silenced miR-210-3p-overexpressed bone marrow-derived macrophages induce glucose intolerance and IR in lean mice. Mechanistically, miR-210-3p interacts with the 3'-UTR of GLUT4 mRNA and silences its expression, compromising cellular glucose uptake and insulin sensitivity. Therapeutic inhibition of miR-210-3p in VAT notably rescues high-fat diet-fed mice from obesity-induced systemic glucose intolerance. Thus, targeting adipose tissue macrophage-specific miR-210-3p during obesity could be a promising strategy for managing IR and type 2 diabetes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction., Methods: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction., Results: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively., Conclusion: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction., (© 2024. The Author(s).)

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.

Background: Obesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP., Method: The body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test., Results: Patients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678-0.784., Conclusions: This study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP., (© 2024. The Author(s).)

Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and incident NAFLD in 2830 participants (1205 males and 1625 females) aged 55-70 years. During a 4.6-year median follow-up, the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in females. Further analyses showed that the above-mentioned positive associations were stronger in males than in females, especially in participants under 60 years old. In contrast, these sex differences disappeared in those over 60 years old. Furthermore, the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific pattern. Additionally, sex-specific potential mediators, such as insulin resistance, lipid metabolism, inflammation, and adipokines, may exist in the associations between adipose tissue and NAFLD. This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age, highlighting the potential need for sex- and age-specific management of NAFLD., (© The Author(s) (2023). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Background/aim: To investigate the relationship between sex-related visceral obesity and WHO/ISUP nuclear grade in clear cell renal cell carcinoma (ccRCC)., Materials and Methods: Between January 2018 and June 2022, 95 patients (56 men and 39 women) with pathologically proven ccRCC who underwent abdominal computed tomography examination were retrospectively examined. The patients were classified into two groups: low- and high-WHO/ISUP nuclear grade ccRCC (n = 58 and n = 37), respectively. Patient height, weight, body mass index (BMI), sex, age, subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), and percentage of visceral fat (VF%) were recorded for the two groups., Results: No significant differences were found in age, BMI, SFA, or TFA, but VFA and VF% were significantly higher in the high-grade patient group. In males, maximal tumor diameter (MTD) (67.8% sensitivity and 76.9% specificity) had the highest area under the curve (AUC), while in females, VF% (70.0% sensitivity and 73.7% specificity) had the highest AUC. VF% revealed an odds ratio (OR) of 1.09 in females with high-grade ccRCC, and in males, MTD was an independent predictor of ccRCC with an OR of 1.03., Conclusions: Sex-related body fat tissue, including VFA and VF%, could be used for estimating WHO/ISUP nuclear grade in patients with ccRCC, especially in females., Competing Interests: Conflict of interest: The authors declare that there are no conflicts of interest., (© TÜBİTAK.)

Aim: Few studies have compared the strength in the associations of anthropometric and computed tomography (CT)-based obesity indices with coronary artery calcification (CAC), aortic artery calcification (AoAC), and aortic valve calcification (AVC)., Methods: We assessed cross-sectcional associations of anthropometric and CT-based obesity indices with CAC, AoAC, and AVC. Anthropometric measures included body mass index (BMI), waist circumference, hip ircumference, waist-to-hip circumference ratio, and waist-to-height ratio in 931 men (mean age, 63.7 years) from a population-based cohort. CT images at the L4/5 level were obtained to calculate the areas of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), VAT-to-SAT ratio (VSR), and VAT-to-TAT ratio (VTR). CAC, AoAC, and AVC were quantified using the Agatston score based on CT scanning., Results: CAC, AVC, and AoAC were present in 348 (62.6%), 173 (18.6%), and 769 (82.6%) participants, respectively. In multivariable models adjusting for age, lifestyle factors, and CT types (electron beam CT and multidetector row CT), anthropometric and CT-based obesity indices were positively associated with CAC (p＜0.01). Conversely, VAT-to-SAT ratio and VAT-to-TAT ratio were positively associated with AoAC (p＜0.01). Any obesity indices were not associated with AVC., Conclusions: The strength of the associations of obesity indices with subclinical atherosclerosis varied according to the anatomically distinct atherosclerotic lesions, among men.

Aims: We aim to explore the cumulative predictive value of elevated serum thyroid stimulating hormone (TSH) and visceral fat area (VFA) for metabolic syndrome (MS) development in postmenopausal women., Methods: A total of 1006 postmenopausal females were enrolled in a 10-year prospective longitudinal study from 2011 to 2021 in the community of Banknote Printing Company of Chengdu. The sociodemographic information collection and anthropometric measurements were made by a professional nurse. Fasting blood samples were drawn for chemical analysis of fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and TSH. Magnetic resonance imaging was performed to measure VFA. All the participants were categorized into four groups according to median VFA and serum level of TSH., Results: A total of 793 postmenopausal females without MS underwent a 10-year follow-up study grouping by TSH and VFA: Group 1 (TSH level <4.2 μIU/mL, and VFA < 70 cm 2 ), Group 2 (TSH level ≥4.2 μIU/mL, and VFA < 70 cm 2 ), Group 3 (TSH level <4.2 μIU/mL, and VFA ≥70 cm 2 ) and Group 4 (TSH level ≥4.2 μIU/mL, and VFA ≥70 cm 2 ). During the 10-year follow-up, MS was newly developed in 326 (41.1%) subjects. The incidence of MS was 29.8% (n = 53), 35.2% (n = 63), 41% (n = 87), and 55% (n = 123) from Group 1 to Group 4 (Group 4 vs other groups, p < .001). Cox regression analysis for MS prediction demonstrated that both TSH (Model 3, hazard ratio [HR] = 1.07 [95% confidence interval, 1.05-1.09]) and VFA (Model 4, HR = 1.02 [95% confidence interval, 1.01-1.08]) were not only independent predictors of MS but also involved some interaction between each other (p for interaction = .021)., Conclusion: Our findings suggested that mutual interaction between higher TSH and VFA contributed to the development of MS. Further studies are needed to clarify these contributions., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: In patients diagnosed with sarcopenia, the presence of chronic preoperative inflammation, assessed by the ratio of the visceral fat area (VFA) to the total abdominal muscle area index (TAMAI) (VFA/TAMAI), has been found to adversely affect wound healing. An elevated VFA/TAMAI may contribute to a higher incidence of postoperative recurrent fistulas (RFs) following definitive surgery (DS) for small intestinal fistulas accompanied by diffuse extensive abdominal adhesions. The objective of this study was to evaluate the predictive value of VFA/TAMAI for postoperative RFs., Methods: The study enrolled 183 sarcopenic patients, with a median age of 51 years [interquartile range (IQR): 38-61 years), a median body mass index of 19.6 kg/m 2 (IQR: 18.9-21.0 kg/m 2 ) who underwent DS for small intestinal fistulas between January 2018 and October 2022 were included in the multicenter study. The outcomes assessed were RFs and postoperative length of stay (LOS). VFA/TAMAI was examined as a potential risk factor for each outcome., Results: Out of the 183 patients, 20.2% ( n =37) developed RFs. The multivariate regression analysis identified VFA/TAMAI as the sole factor associated with RFs [odds ratio=1.78, 95% confidence interval (CI): 1.09-2.87, P =0.02]. The multivariable Cox regression analysis demonstrated that an elevated VFA/TAMAI was linked to a reduced postoperative LOS (hazard ratio=0.69, 95% CI: 0.59-0.81, P <0.001)., Conclusion: In sarcopenic patients, a high VFA/TAMAI predicated the occurrence of RFs after DS for small intestinal fistulas in the presence of diffuse extensive abdominal adhesions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota., Methods: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46., Results: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups., Conclusions: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

There is no computed tomography (CT)-based numerical index for predicting Cushing's syndrome (CS) in patients with adrenal incidentalomas. We tested the hypothesis that the iliopsoas muscle (Ip-M) to visceral fat (V-fat) ratio (IVR) on CT may predict CS in elderly female patients with adrenal tumors. We examined the V-fat area, subcutaneous fat (S-fat) area, Ip-M area, V-fat/S-fat ratio, and IVR at the third lumbar vertebra (L3) level using abdominal CT in female patients aged ≥50 years with cortisol-producing adrenal tumor diagnosed with CS or non-functioning adrenal tumor (NFT) in the derivation cohort. We performed receiver operating characteristic (ROC) analysis to evaluate the diagnostic value of the V-fat/S-fat ratio and IVR for predicting CS. We assessed the usefulness of the IVR in a separate validation cohort. In the derivation cohort, the IVR was significantly lower in the 9 patients with CS than in the 15 patients with NFT (p < 0.001). In ROC analysis with a cut-off value of 0.067, the IVR showed a sensitivity of 100%, specificity of 80.0%, positive likelihood ratio (PLR) of 5.000, and negative likelihood ratio (NLR) of 0.000. The area under the curve was significantly higher for the IVR than for the V-fat/S-fat ratio (0.933 vs. 0.704, respectively, p = 0.036). In 23 patients in the validation cohort, the IVR demonstrated a PLR of 5.714 and an NLR of 0.327. The novel IVR index, based on single-slice CT at the L3 level, predicted CS in elderly female patients with adrenal tumors.

Body fat is stored in anatomically distinct adipose depots that vary in their cell composition and play specialized roles in systemic metabolic homeostasis via secreted products. Their local effects on nearby tissues (e.g. the gut and visceral adipose tissues) are increasingly recognized and this local crosstalk is being elucidated. The major subcutaneous fat depots, abdominal and gluteal-femoral, exert opposite effects on the risk of metabolic disease. The pace of research into developmental, sex, and genetic determinants of human adipose depot growth and function is rapidly accelerating, providing insight into the pathogenesis of metabolic dysfunction in persons with obesity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The prognostic role of increased visceral fat attenuation (VFA) remains underexplored. We investigated the long-term prognostic implications of computed tomography (CT)-derived VFA in a health check-up population., Methods: This study included consecutive individuals who had positron-emission tomography/CT scans for health check-ups between January 2004 and December 2010. The primary outcome was overall survival (OS), and the secondary outcomes were cancer-specific survival (CSS) and non-cancer-specific survival (NCS). Commercially available body composition analysis software was used to obtain abdominal waist VFA, visceral fat volume index (VFI) and skeletal muscle index (SMI) at the L3 level. Sarcopenia was determined using sex-specific SMI references. VFA and VFI were dichotomized using the thresholds for the highest quartiles. The relationship between CT-derived body composition parameters and body mass index (BMI) was evaluated with Pearson correlation coefficients. The prognostic implications of VFA and sarcopenic obesity (SO) defined by VFA were assessed by multivariable Cox regression analysis and Kaplan-Meier plots with log-rank tests., Results: A total of 2720 individuals (1530 men [56.3%] and 1190 women [43.7%]; median age: 53 years, inter-quartile range: 47-60 years) were included. During the median follow-up of 138 months, 128 individuals (5%) died (cancer mortality: 2%; non-cancer mortality: 3%), with 0.2% (5 of 2720) and 1.1% (30 of 2720) of 1- and 5-year mortality rates. VFA was negatively correlated with BMI (r = -0.62; P < 0.001) and VFI (r = -0.69; P < 0.001). After adjusting for clinical variables, sarcopenia and VFI, high VFA was a negative prognostic factor for OS (hazard ratio [HR]: 1.05 per Hounsfield unit; 95% confidence interval [CI]: 1.02, 1.08; P = 0.001), CSS (HR: 1.07 per Hounsfield unit; 95% CI: 1.02, 1.12; P = 0.006) and NCS (HR: 1.03 per Hounsfield unit; 95% CI: 1.01, 1.06; P = 0.009). Individuals with high VFA had higher high-sensitivity C-reactive protein levels than those with low VFA (0.11 vs. 0.03 mg/dL; P < 0.001). Individuals with SO defined by VFA had worse OS (9% vs. 4%; P < 0.001), CSS (3% vs. 2%; P = 0.02) and NCS (6% vs. 3%; P < 0.001) than those without SO, even in the same BMI (underweight-to-normal BMI, OS: 8% vs. 4%; overweight-to-obese BMI, OS: 38% vs. 4%; P < 0.001 in both) or VFI category (high VFI, OS: 43% vs. 6%; low VFI, OS: 8% vs. 3%; P < 0.001 in both)., Conclusions: High VFA was associated with long-term mortality and low-grade inflammation. VFA can further stratify the current SO by BMI or VFI, and SO defined by VFA can identify individuals who are most vulnerable to long-term mortality., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: The preoperative prediction of peritoneal metastasis (PM) in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan., Aim: To explore the predictive value of visceral fat (VF) parameters obtained from preoperative computed tomography (CT) images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma (GC)., Methods: A total of 128 confirmed GC cases (84 male and 44 female patients) that underwent CT scans were analyzed and categorized into PM-positive ( n = 43) and PM-negative ( n = 85) groups. The clinical characteristics and VF parameters of two regions of interest (ROIs) were collected. Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM. Prediction models with and without VF parameters were established by multivariable logistic regression analysis., Results: The mean attenuations of VF ROI 1 and VF ROI 2 varied significantly between the PM-positive and PM-negative groups ( P = 0.044 and 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) of VF ROI 1 and VF ROI 2 were 0.599 and 0.657, respectively. The mean attenuation of VF ROI 2 was included in the final prediction combined model, but not an independent risk factor of PM ( P = 0.068). No significant difference was observed between the models with and without mean attenuation of VF (AUC: 0.749 vs 0.730, P = 0.339)., Conclusion: The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Intra-abdominal fat volume (IFV) has been shown to have a negative impact on surgical outcomes in gastric cancer (GC) and other gastrointestinal surgeries. The purpose of this study is to look into the relationship between IFV and perioperative outcomes in GC patients using multi-detector rows computed tomography (MDCT) and assess the importance of implementing this observation in current surgical fellowship training programs., Methods: Patients with GC who underwent open D2 gastrectomy between May 2015 and September 2017 were included in the study. Based on MDCT estimation, patients were divided into high IFV (IFV ≥ 3,000 ml) and low IFV (IFV < 3,000 ml) groups. Perioperative outcomes for cancer staging, type of gastrectomy, intraoperative blood loss (IBL), anastomotic leakage, and hospital stay were compared between the two groups. This study was registered as CTR2200059886., Results: Out of 226 patients, 54 had early gastric carcinoma (EGC), while 172 had advanced gastric carcinoma (AGC). There were 64 patients in the high IFV group and 162 in the low IFV group. The high IFV group had significantly higher IBL mean values ( p = 0.008). Therefore, having a high IFV was a risk factor for the occurrence of perioperative complications ( p = 0.008)., Conclusions: High IFV estimated by MDCT prior to GC surgery was associated with increased IBL and postoperative complications. Incorporating this CT-IFV estimation into surgical fellowship programs may aid aspiring surgeons in selecting patients during independent practice in their learning curve and surgical practice for the most appropriate approach for treating GC patients., Competing Interests: Tian Li is an Academic Editor for PeerJ., (©2023 Shah et al.)

Introduction: Obesity affects cardiac geometry, causing both eccentric (due to increased cardiac output) and concentric (due to insulin resistance) remodelling. Following bariatric surgery, reversal of both processes should occur. Furthermore, epicardial adipose tissue loss following bariatric surgery may reduce pericardial restraint, allowing further chamber expansion. We investigated these changes in a serial imaging study of adipose depots and cardiac geometry following bariatric surgery., Methods: 62 patients underwent cardiac magnetic resonance (CMR) before and after bariatric surgery, including 36 with short-term (median 212 days), 37 medium-term (median 428 days) and 32 long-term (median 1030 days) follow-up. CMR was used to assess cardiac geometry (left atrial volume (LAV) and left ventricular end-diastolic volume (LVEDV)), LV mass (LVM) and LV eccentricity index (LVei - a marker of pericardial restraint). Abdominal visceral (VAT) and epicardial (EAT) adipose tissue were also measured., Results: Patients on average had lost 21kg (38.9% excess weight loss, EWL) at 212 days and 36kg (64.7% EWL) at 1030 days following bariatric surgery. Most VAT and EAT loss (43% and 14%, p<0.0001) occurred within the first 212 days, with non-significant reductions thereafter. In the short-term LVM (7.4%), LVEDV (8.6%) and LAV (13%) all decreased (all p<0.0001), with change in cardiac output correlated with LVEDV (r=0.35,p=0.03) and LAV change (r=0.37,p=0.03). Whereas LVM continued to decrease with time (12% decrease relative to baseline at 1030 days, p<0.0001), both LAV and LVEDV had returned to baseline by 1030 days. LV mass:volume ratio (a marker of concentric hypertrophy) reached its nadir at the longest timepoint (p<0.001). At baseline, LVei correlated with baseline EAT (r=0.37,p=0.0040), and decreased significantly from 1.09 at baseline to a low of 1.04 at 428 days (p<0.0001). Furthermore, change in EAT following bariatric surgery correlated with change in LVei (r=0.43,p=0.0007)., Conclusions: Cardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to pre-operative sizes by 1030 days. We propose this is due to an initial reversal of eccentric remodelling followed by reversal of concentric remodelling. Furthermore, we provide evidence for a role of EAT contributing to pericardial restraint, with EAT loss improving markers of pericardial restraint., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Henry, Abdesselam, Deal, Lewis, Rayner, Bernard, Dutour, Gaborit, Kober, Soghomonian, Sgromo, Byrne, Bege, Neubauer, Borlaug and Rider.)

Background: The intra-abdominal cavity, surrounded by adipocytes, is the main metastatic site of epithelial ovarian, fallopian tube, and peritoneal cancer. Epidemiological and molecular studies have demonstrated a link between adipose tissue and ovarian cancer. However, the clinical significance of fatty tissue has not been elucidated. Thus, we investigated the clinical significance of body composition in patients with epithelial ovarian, fallopian tube, and peritoneal cancer., Methods: Fat and skeletal muscle areas were measured using software based on pretreatment computed tomography scans at the third lumbar vertebra. Fat-to-muscle ratios were calculated using the total (visceral and subcutaneous) fat area or visceral fat area. High fat-to-muscle ratios were defined by values greater than the mean. Sarcopenia was defined as a skeletal muscle index < 38.7 cm 2 /m 2 . The clinicopathological parameters and survival of 153 patients were analyzed., Results: High visceral fat-to-muscle ratios and sarcopenia at the time of diagnosis were observed in 43.8% and 33.3% of the patients, respectively. Multivariate analysis showed that high visceral fat-to-muscle ratio (p = 0.014), advanced Federation of Gynecology and Obstetrics stage (p = 0.008), and chemoresistance (p = 0.027) were independent factors for worse overall survival. Patients with high visceral fat-to-muscle ratios were older, had higher body mass indexes, and were more likely to have diabetes/hypertension, serous cancer subtypes, and implementation of neoadjuvant chemotherapy than those with low visceral fat-to-muscle ratios. The platelet count was significantly higher in the high visceral fat-to-muscle ratio group than in the low visceral fat-to-muscle ratio group (p = 0.011)., Conclusions: Pretreatment visceral fat area could be an independent predictive factor of overall survival in patients with epithelial ovarian, fallopian tube, and peritoneal cancer and may be significantly associated with thrombocytosis., (© 2023. The Author(s).)

Introduction: We explored whether visceral fat accumulation mediates the development of hepatic steatosis in individuals living with overweight and obesity., Methods: This cross-sectional study enrolled 769 outpatients with overweight and obesity aged 18-65 years. The controlled attenuation parameter (CAP) was used to quantify the degree of hepatic steatosis. Visceral fat accumulation, represented by the visceral fat area (VFA), was measured using magnetic resonance imaging. The associations of body mass index (BMI), VFA, and CAP with each other were assessed by univariate analysis, multivariate linear regression, and mediation analysis, respectively., Results: Compared with women, male subjects had higher BMI, VFA, and CAP levels. In both sex, CAP was positively correlated with BMI and VFA by the univariate analysis. After adjusting for demographic and serum characteristics, the linear correlation coefficients between BMI and CAP were 1.738 (95% confidence interval (CI): 1.100, 2.377), 1.524 (95% CI: 0.798, 2.249), and 2.650 (95% CI: 1.292, 4.009) in all subjects, females, and males, respectively, while those between VFA and CAP were 0.190 (95% CI: 0.133, 0.247), 0.184 (95% CI: 0.117, 0.252), and 0.194 (95% CI: 0.086, 0.301). Mediation analysis showed that visceral fat accumulation contributed to 51.37%, 53.85%, and 26.51% of obesity-induced hepatic steatosis in the total, female, and male subjects, respectively., Conclusion: Visceral fat accumulation partially mediates obesity-induced hepatic steatosis in individuals with overweight and obesity, especially in women. More focus on visceral fat reduction is needed in individuals with obesity., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Middle Eastern immigrants are at high-risk for insulin resistance. Fatty acid composition (FAC) plays an important role in the development of insulin resistance but has not been investigated in people of Middle Eastern ancestry. Here, the aim was to assess the FAC in visceral and subcutaneous adipose tissue (VAT and SAT) in healthy Iraqi- and Swedish-born men using a magnetic resonance imaging (MRI) method.This case-control study included 23 Iraqi- and 15 Swedish-born middle-aged men, without cardiometabolic disease. Using multi-echo MRI of the abdomen, the fractions of saturated, monounsaturated, and polyunsaturated fatty acids (fSFA, fMUFA, and fPUFA) were estimated in VAT and SAT. SAT was further analyzed in deep and superficial compartments (dSAT and sSAT).In all depots, fPUFA was significantly higher and fSFA significantly lower in Iraqi men, independently of age and BMI. In both Iraqi- and Swedish-born men, higher fPUFA and lower fMUFA were found in sSAT vs. dSAT. Among Iraqi men only, higher fPUFA and lower fMUFA were found in SAT vs. VAT.Iraqi-born men presented a more favorable abdominal FAC compared to Swedish-born men. This MRI method also revealed different FACs in different abdominal depots. Our results may reflect a beneficial FAC in Middle Eastern immigrants.

Clear cell renal carcinoma (ccRCC) is the most common histological type of renal cancer and has the highest mortality. Several studies have been conducted on the relationship between adipose tissue and ccRCC prognosis, however, the results have been inconsistent to date. The current study aimed at establishing a link between abdominal fat composition and short-term prognosis in patients with ccRCC after T-stage stratification. We retrospectively analysed 250 patients with pathologically confirmed ccRCC (173 low T-stage and 77 high T-stage) in our hospital. The computed tomography (CT) images were evaluated using ImageJ. Then, subcutaneous and visceral fat areas (SFA and VFA), total fat areas (TFA) and the relative VFA (rVFA) were measured and computed. Meanwhile, biochemical indices of blood serum were analysed. The results showed that rVFA in low T-stage cohort who had a history of short-term postoperative complications were significantly lower than those who did not. No such association was observed in the high T-stage cohort. Further investigation revealed that the correlations between biochemical indexes and fat area-related variables varied across T-stage groups. As a result, rVFA is a reliable independent predictor of short-term prognosis in patients with low T-stage ccRCC but not in patients with high T-stage ccRCC.

Cancer cachexia, a paraneoplastic syndrome characterized by ongoing skeletal muscle mass loss, is accompanied by adipose tissue loss and strongly affects chemotherapy endurance. Our aim was to detect a serum marker reflecting pancreatic cancer cachexia and predicting subsequent loss of muscle mass and adipose tissue, focusing on adipose tissue-secreted proteins. Murine-derived pancreatic cancer cells were orthotopically injected into the mouse pancreatic tail. After 3 weeks, RNA sequencing of perigonadal fat and orthotopic tumors was carried out. We analyzed stocked sera and clinical data of metastatic pancreatic cancer patients who received chemotherapy. Perigonadal fat weight/body weight decreased in mice with orthotopic tumors compared to those without tumors. By RNA sequencing and real-time PCR validation, pentraxin 3 (PTX3) was identified as a secreted protein-encoded gene whose expression was significantly higher in the perigonadal fat of mice with orthotopic tumors than in that of mice without orthotopic tumors and was least expressed in orthotopic tumors. Serum PTX3 levels correlated with PTX3 mRNA levels in perigonadal fat and were higher in mice with orthotopic tumors than in those without tumors. In 84 patients diagnosed with metastatic pancreatic cancer, patients with high serum PTX3 levels showed a greater visceral fat loss/month and skeletal muscle mass index (SMI) decrease/month than those with low serum PTX3 levels. High serum PTX3 was an independent risk factor for visceral fat loss, decreased SMI, and poor prognosis. High serum PTX3 in pancreatic cancer patients predicts visceral fat and muscle mass loss and major clinical outcomes of cancer cachexia., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background/aim: Body composition assessment has shown promising results as a prognostic biomarker as depicted by cross-sectional imaging of several tumor entities including lymphomas. The present study sought to elucidate the prognostic relevance of subcutaneous and visceral fat tissue (SAT and VAT) in patients with primary central nervous system lymphoma (PCNSL)., Patients and Methods: Overall, 74 patients (36 female patients, 46.7%) with a mean age of 64.2±12.8 years (range=23-81 years) were identified in the database with sufficient clinical and imaging data and included into this retrospective study. Fat area assessment was performed on one axial slide on L3-height derived from staging computed tomography (CT) images. Subcutaneous, visceral, and intramuscular adipose tissues (SAT, VAT, IMAT) were estimated. Also, density of SAT, VAT, and IMAT were estimated. Finally, the ratio VAT/SAT (VSR) was calculated. Overall and progression-free survival (OS and PFS) were used as study end points., Results: In the observation period, overall, 47 patients (63.5%) died. Mean OS was 33.8±45.4 months and mean PFS was 26.6±42.7 months. The mean VAT value was 162±99.5 cm 2 , the mean SAT was 202.4±103.3 cm 2 , the mean VSR was 0.92±0.69. The hazard ratios (HRs) for overall survival were 0.87 for high VAT, 1.52 for SAT, and 0.73 for VSR in univariable analysis. For PFS it was 0.24 for VAT, 1.11 for SAT, and 1.07 for VSR. No values achieved statistical significance. Similar results were shown in Kaplan-Meier analysis for OS and PFS, respectively., Conclusion: Parameters of adipose tissue are not associated with OS and PFS in patients with PCNSL., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Colorectal cancer (CRC) is a major health problem worldwide, with an estimated 1.9 million new cases and 915,880 deaths in 2020 alone. The etiology of CRC is complex and involves both genetic and lifestyle factors. Obesity is a major risk factor for CRC, and the mechanisms underlying this link are still unclear. However, the generalized inflammatory state of adipose tissue in obesity is thought to play a role in the association between CRC risk and development. Visceral adipose tissue (VAT) is a major source of proinflammatory cytokines and other factors that contribute to the characteristic systemic low-grade inflammation associated with obesity. VAT is also closely associated with the tumor microenvironment (TME), and recent evidence suggests that adipocytes within the TME undergo phenotypic changes that contribute to tumor progression. In this review, we aim to summarize the current evidence linking obesity and CRC, with a focus on the role of VAT in tumor etiology and progression.

Background: Obesity is a growing problem worldwide, especially in countries with improved socioeconomic circumstances. Also, in the Netherlands the incidence of overweight and obesity is rising. There is increasing evidence on the association between obesity and tumorigenesis. Of all cancer types, endometrial cancer (EC) has the strongest positive correlation with obesity. Obesity is generally defined as a body mass index (BMI) >30, yet does not cover the differences in fat distribution in visceral and subcutaneous compartments. Visceral fat is assumed to be relatively more metabolically active and likely negative prognostic biomarker in non-endometrioid EC. Whereas subcutaneous fat is mainly responsible for oestrogen production through increased aromatase activity., Objective: The aim of this study is to compare hormone levels and inflammatory markers after bilateral salpingo-oophorectomy (BSO) in obese and non-obese patients. Secondary objectives are to compare the effect of fat distribution and diagnosis (benign vs. EC) on the observed changes in hormone levels and inflammatory markers, and to compare the effect of BSO on menopausal complaints., Methods: Prospective multicentre observational cohort study. A total of 160 patients will be included, of which 80 patients with a normal BMI (18-25 kg/m2) and 80 patients with an obese BMI >32-35 kg/m2. Preoperative abdominal CT will be performed and fasting venous blood samples are obtained for hormone levels and inflammation markers analysis. During surgery, adipose tissue biopsies of subcutaneous and visceral (omental and intestinal epiploic fat) compartments will be collected and stored fresh frozen. In addition a fasting blood draw six weeks after surgery will be obtained. All subjects will fill in two questionnaires before surgery and one after surgery., Discussion: We hypothesize that BMI, the type of fat distribution, and possibly the underlying pathology significantly influence in hormone levels, and systemic inflammation changes after BSO. Previous studies have found several clues for a relationship between obesity and endometrial cancer. We expect that our study will contribute to pinpoint the exact differences between 'healthy obesity' and 'unhealthy obesity' and will help to identify patients that are more at risk of developing cancer (or possibly suffer from other related problems such as cardiovascular problems e.g.)., Competing Interests: The authors have declared that no competing interests exist.

Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.

A variety of axes between brain and abdominal organs have been reported, but the interaction between brain and visceral white adipose tissue (vWAT) remains unclear. In this review, we summarized human studies on the association between brain and vWAT, and generalized their interaction and the underlying mechanisms according to animal and cell experiments. On that basis, we come up with the concept of the brain-vWAT axis (BVA). Furthermore, we analyzed the potential mechanisms of involvement of BVA in the pathogenesis of Alzheimer's disease (AD), including vWAT-derived fatty acids, immunological properties of vWAT, vWAT-derived retinoic acid and vWAT-regulated insulin resistance. The proposal of BVA may expand our understanding to some extent of how the vWAT impacts on brain health and diseases, and provide a novel approach to study the pathogenesis and treatment strategies of neurodegenerative disorders., Competing Interests: Declaration of interests The authors confirm that there are no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The clinical difference between nonalcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) between the two sexes is unclear. This study aimed to determine the influences of alcohol consumption and qualitative abdominal fat between male and female patients with NAFLD and MAFLD. This cross-sectional study examined 11,766 participants who underwent health check-ups comparing lifestyle habits, biochemical features, and noninvasive liver fibrosis scores, between non-MAFLD and MAFLD groups. Furthermore, differences in alcohol consumption and qualitative abdominal fat were examined between male and female patients with NAFLD and MAFLD. The prevalence of metabolic dysregulation, ratio of visceral fat area to subcutaneous fat area, and noninvasive liver fibrosis scores were significantly higher in male patients with MAFLD than in those with NAFLD (p < 0.05), but these were not significantly different in female patients. Among male patients with an alcohol consumption of > 70 g/week, several noninvasive liver fibrosis scores were significantly higher in the MAFLD group than in the NAFLD group (all p < 0.05). The influences of alcohol consumption and qualitative abdominal fat on NAFLD and MAFLD were different between sexes. The development of liver fibrosis should be considered in male patients with MAFLD who exceed mild drinking., (© 2022. The Author(s).)

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value.

Objective: Type 2 diabetes (T2D) is associated with significant end-organ damage and ectopic fat accumulation. Multiparametric magnetic resonance imaging (MRI) can provide a rapid, noninvasive assessment of multiorgan and body composition. The primary objective of this study was to investigate differences in visceral adiposity, ectopic fat accumulation, body composition, and relevant biomarkers between people with and without T2D., Methods: Participant demographics, routine biochemistry, and multiparametric MRI scans of the liver, pancreas, visceral and subcutaneous adipose tissue, and skeletal muscle were analyzed from 266 participants (131 with T2D and 135 without T2D) who were matched for age, gender, and BMI. Wilcoxon and χ 2 tests were performed to calculate differences between groups., Results: Participants with T2D had significantly elevated liver fat (7.4% vs. 5.3%, p = 0.011) and fibroinflammation (as assessed by corrected T1 [cT1]; 730 milliseconds vs. 709 milliseconds, p = 0.019), despite there being no differences in liver biochemistry, serum aspartate aminotransferase (p = 0.35), or alanine transaminase concentration (p = 0.11). Significantly lower measures of skeletal muscle index (45.2 cm 2 /m 2 vs. 50.6 cm 2 /m 2 , p = 0.003) and high-density lipoprotein cholesterol (1.1 mmol/L vs. 1.3 mmol/L, p < 0.0001) were observed in participants with T2D., Conclusions: Multiparametric MRI revealed significantly elevated liver fat and fibroinflammation in participants with T2D, despite normal liver biochemistry. This study corroborates findings of significantly lower measures of skeletal muscle and high-density lipoprotein cholesterol in participants with T2D versus those without T2D., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

Adrenal incidentalomas are incidentally discovered adrenal masses greater than one centimeter in diameter. An association between insulin resistance and adrenal incidentalomas has been established. However, the pathophysiological link between these two conditions remains incompletely characterized. This review examines the literature on the interrelationship between insulin resistance and adrenal masses, their subtypes, and related pathophysiology. Some studies show that functional and non-functional adrenal masses elicit systemic insulin resistance, whereas others conclude the inverse. Insulin resistance, hyperinsulinemia, and the anabolic effects on adrenal gland tissue, which have insulin and insulin-like growth factor-1 receptors, offer possible pathophysiological links. Conversely, autonomous adrenal cortisol secretion generates visceral fat accumulation and insulin resistance. Further investigation into the mechanisms and timing of these two pathologies as they relate to one another is needed and could be valuable in the prevention, detection, and treatment of both conditions.

Context: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities., Objective: Here we aim to compare the proteomic profiles of mature adipocytes from different depots., Methods: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data., Results: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA., Conclusion: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Pancreatic ductal adenocarcinoma (PDAC) patients display distinct phenotypes of cachexia development, with either adipose tissue loss preceding skeletal muscle wasting or loss of only adipose tissue. Activin A levels were measured in serum and analyzed in tumor specimens of both a cohort of Stage IV PDAC patients and the genetically engineered KPC mouse model. Our data revealed that serum activin A levels were significantly elevated in Stage IV PDAC patients in comparison to age-matched non-cancer patients. Little is known about the role of activin A in adipose tissue wasting in the setting of PDAC cancer cachexia. We established a correlation between elevated activin A and remodeling of visceral adipose tissue. Atrophy and fibrosis of visceral adipose tissue was examined in omental adipose tissue of Stage IV PDAC patients and gonadal adipose tissue of an orthotopic mouse model of PDAC. Remarkably, white visceral adipose tissue from both PDAC patients and mice exhibited decreased adipocyte diameter and increased fibrotic deposition. Strikingly, expression of thermogenic marker UCP1 in visceral adipose tissues of PDAC patients and mice remained unchanged. Thus, we propose that activin A signaling could be relevant to the acceleration of visceral adipose tissue wasting in PDAC-associated cachexia., (© 2022. The Author(s).)

Background/aims: Previous studies have investigated the relationship between visceral obesity and the risk of colorectal tumors. Visceral obesity may affect the outcome of colorectal cancer (CRC), including survival and metastasis. We investigated the associations between visceral adipose tissue and oncologic outcomes in stage III CRC., Methods: Four hundred seventy-two patients with stage III CRC were identified. Subcutaneous and visceral adipose tissue areas were measured volumetrically via computed tomography for each patient at different levels of the lumbar spine. After adjusting for age, sex, and other clinical factors, the effects of visceral adipose tissue area on mortality and recurrence were assessed using Cox proportional hazard regression., Results: In univariate and multivariate analyses, a higher visceral adipose tissue to total adipose tissue (VT) ratio (hazard ratio [HR], 1.041; 95% CI, 1.008 to 1.075; p=0.015) and higher visceral adipose tissue to subcutaneous adipose tissue (VS) ratio (HR, 1.016; 95% CI, 1.005 to 1.028; p=0.006) were both associated with poor CRC-specific survival. Interestingly, in the evaluation of each site of recurrence, a higher VT ratio (HR, 1.069; 95% CI, 1.010 to 1.131; p=0.020) and higher VS ratio (HR, 1.024; 95% CI, 1.003 to 1.045; p=0.023) were both related to a higher risk of peritoneal seeding and tumor recurrence. The VT ratio at the L3-L4 level was significantly associated with a higher risk of peritoneal seeding and tumor recurrence (HR, 4.969; 95% CI, 1.303 to 18.949; p=0.019), while other levels showed no such relationship., Conclusions: Visceral obesity is closely related to increased risks of CRC-specific mortality and peritoneal seeding metastasis in stage III CRC patients.

Context: Chronic glucocorticoid (GC) overexposure, resulting from endogenous Cushing's syndrome (CS) or exogenous GC therapy, causes several adverse outcomes, including persistent central fat accumulation associated with a low-grade inflammation. However, no previous multiomics studies in visceral adipose tissue (VAT) from patients exposed to high levels of unsuppressed GC during active CS or after remission are available yet., Objective: To determine the persistent VAT transcriptomic alterations and epigenetic fingerprints induced by chronic hypercortisolism., Methods: We employed a translational approach combining high-throughput data on endogenous CS patients and a reversible CS mouse model. We performed RNA sequencing and chromatin immunoprecipitation sequencing on histone modifications (H3K4me3, H3K27ac, and H3K27me3) to identify persistent transcriptional and epigenetic signatures in VAT produced during active CS and maintained after remission., Results: VAT dysfunction was associated with low-grade proinflammatory status, macrophage infiltration, and extracellular matrix remodeling. Most notably, chronic hypercortisolism caused a persistent circadian rhythm disruption in VAT through core clock genes modulation. Importantly, changes in the levels of 2 histone modifications associated to gene transcriptional activation (H3K4me3 and H3K27ac) correlated with the observed differences in gene expression during active CS and after CS remission., Conclusion: We identified for the first time the persistent transcriptional and epigenetic signatures induced by hypercortisolism in VAT, providing a novel integrated view of molecular components driving the long-term VAT impairment associated with CS., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood., Objective: We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and increased adiponectin ubiquitination and degradation, caused by inflammation and endoplasmic reticulum (ER) stress., Methods: Visceral adipose tissues were collected from lean and obese pregnant humans and mice. Total and ubiquitinated adiponectin, and markers of inflammation, ER stress, and insulin resistance were examined in adipose tissues. The role of insulin, inflammation, and ER stress in mediating adiponectin ubiquitination and degradation was examined using 3T3L-1 adipocytes., Results: Obesity in pregnancy is associated with adipose tissue inflammation, ER stress, insulin resistance, increased adiponectin ubiquitination, and decreased total abundance of adiponectin. Adiponectin ubiquitination was increased in visceral fat of obese pregnant women as compared to lean pregnant women. We further observed that insulin prevents, whereas ER stress and inflammation promote, adiponectin ubiquitination and degradation in differentiated 3T3-L1 adipocytes., Conclusion: We have identified adiponectin ubiquitination as a key mechanism by which obesity diminishes adiponectin secretion in pregnancy. This information will help us better understand the mechanisms controlling maternal insulin resistance and fetal growth in pregnancy and may provide a foundation for the development of strategies aimed at improving adiponectin production in pregnant women with obesity or gestational diabetes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The relationship between visceral adiposity index (VAI) and unhealthy metabolic phenotype remained unclear in children and adolescents. This study aimed to investigate their association and compared the ability of VAI and traditional adiposity indicators (body mass index, waist circumference and waist-to-height ratio) to predict metabolically unhealthy phenotype among normal-weight, overweight and obese children and adolescents. In this cross-sectional study, 1722 children and adolescents aged 12-18 years were selected by cluster random sampling, underwent a questionnaire survey, physical examination and biochemical tests. Participants were divided into four phenotypes according to the combination of the weight status determined by body mass index (BMI) and metabolic syndrome components. Receiver operating characteristic (ROC) analysis and multivariate logistic regression were used to compare the predictive capacity between VAI and traditional adiposity indicators and their relationship with metabolically unhealthy phenotype. We found that VAI had better performance in predicting metabolically unhealthy phenotype than traditional adiposity indicators, the area under the receiver-operating characteristic curve (AUC) were 0.808 and 0.763 for boys and girls with normal-weight, 0.829 and 0.816 for boys and girls with overweight and obese (all P < 0.001). VAI was most strongly related to metabolically unhealthy phenotype whether or not to adjust the age, the adjusted OR and 95%CI was 6.15 (4.13-9.14) in boys with normal weight, and 5.90 (3.06-11.36), 4.95 (2.35-10.41) in boys and girls with overweight and obese, respectively (all P < 0.001). Our findings suggested VAI could be used as a comprehensive predictor to identify unhealthy metabolic phenotype in children and adolescents., (© 2021. The Author(s).)

Although much is known about how adipose tissue affects the development of clear cell renal carcinoma (ccRCC), little information is available for the utility of sex-specific abdominal visceral fat composition as a predictor of clear cell renal carcinoma (ccRCC) T stage. We conducted CT-based sex-specific abdominal fat measurements in ccRCC patients to assess whether VFA distribution could predict the ccRCC T stage. In total, 253 patients (182 males and 71 females) from our hospital with pathologically confirmed ccRCC (178 low T-stage and 75 high T-stage) were retrospectively reviewed for the present study. Computed tomography (CT) scans were assessed using ImageJ to differentiate between the visceral and subcutaneous fat areas (VFA and SFA), after which the relative VFA (rVFA) and total fat area (TFA) were computed. The relationships between these fat area-related variables, patient age, sex, and BMI, and ccRCC T stage were then evaluated through univariate and multivariate logistic regression analysis to clarify the association between general or sex-specific abdominal visceral fat and T stage. Following adjustment for age, males with high T stage ccRCC exhibited an increased rVFA as compared to males with low T stage ccRCC, with the same relationship being observed among females. This association between rVFA and high T stage was confirmed through both univariate and multivariate models. As thus, sex-specific visceral fat composition is a reliable independent predictor that can identify both male and female patients with high T stage ccRCC.