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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(7): 1004-1010, 2024 Jul 06.
Article in Chinese | MEDLINE | ID: mdl-39034784

ABSTRACT

Objective: To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13+6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results: A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [RR(95%CI): 1.34 (1.08-1.67)], and 61% [RR(95%CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [RR(95%CI): 1.42 (1.22-1.65)] and 70% [RR(95%CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old (P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m2, and the GDM risk increased by 57% [RR(95%CI): 1.57 (1.22-2.04)] in Q3 and 65% [RR(95%CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion: High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.


Subject(s)
Diabetes, Gestational , Intra-Abdominal Fat , Intra-Abdominal Fat/anatomy & histology , Intra-Abdominal Fat/pathology , Diabetes, Gestational/epidemiology , Diabetes, Gestational/pathology , China/epidemiology , Pregnancy Trimester, First , Cohort Studies , Humans , Female , Pregnancy , Adult , Body Mass Index , Incidence , Risk Factors
2.
Front Endocrinol (Lausanne) ; 15: 1434333, 2024.
Article in English | MEDLINE | ID: mdl-39040678

ABSTRACT

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 (ß=0.098, P=0.036) and women (ß=0.099, P=0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men (ß=0.106, P=0.009) and women (ß=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.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Male , Female , Middle Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Atherosclerosis/epidemiology , Atherosclerosis/diagnostic imaging , Risk Factors , Adipose Tissue/diagnostic imaging , Adipose Tissue/pathology , Aged , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , China/epidemiology , Adult , Kidney/pathology , Kidney/diagnostic imaging , Risk Assessment , Tomography, X-Ray Computed
3.
Anticancer Res ; 44(8): 3515-3524, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39060072

ABSTRACT

BACKGROUND/AIM: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex. PATIENTS AND METHODS: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis. RESULTS: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females. CONCLUSION: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival.


Subject(s)
Gastrectomy , Intra-Abdominal Fat , Stomach Neoplasms , Subcutaneous Fat , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnostic imaging , Male , Female , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Middle Aged , Aged , Gastrectomy/mortality , Prospective Studies , Sex Factors , Prognosis , Preoperative Period , Adult , Postoperative Period , Aged, 80 and over , Kaplan-Meier Estimate , Tomography, X-Ray Computed
4.
Ann Endocrinol (Paris) ; 85(3): 226-230, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38871498

ABSTRACT

IMPORTANCE: Epicardial adipose tissue (EAT) is a biologically active organ surrounding myocardium and coronary arteries that has been associated with coronary artery disease (CAD) and atrial fibrillation. Previous work has shown that EAT exhibits beige features. OBJECTIVE: Our objective was to determine whether the stromal vascular fraction of the human EAT contains innate or adaptive lymphoid cells compared to thoracic subcutaneous (thSAT), visceral abdominal (VAT) and subcutaneous abdominal (abSAT). PARTICIPANTS: New pangenomic microarray analysis was performed on previous transcriptomic dataset using significance analysis of microarray and ingenuity pathway analysis (n=41) to identify specific immune signature and its link with browning genes. EAT, thSAT, VAT and abSAT samples from explanted patients with severe cardiomyopathies and multi-organ donor patients (n=17) were used for flow cytometry (FC) immunophenotyping assay. Patients were on average 55±16 years-old; 47% had hypertension and 6% CAD. Phenotypic adaptive and innate immune profiles were performed using a TBNK panel and a specific ILC1-2-3 panel including CD127, CD117, CRTH2 (CD294) and activation markers such as CD25 and CD69. RESULTS: Transcriptomic analysis showed a significant positive correlation between the TH2 immune pathway (IL-4, IL-5, IL-13, IL-25, IL-33) and browning genes (UCP-1, PRDM16, TMEM26, CITED1, TBX1) in EAT versus thSAT (R=0.82, P<0.0001). Regarding adaptive immune cells, a preponderance of CD8T cells, a contingent of CD4T cells, and a few B cells were observed in all ATs (P<0.0001). In innate lymphoid cells (ILCs), an increase was observed in visceral ATs (i.e. EAT; VAT 35±8ILCs/g of tissue) compared to their subcutaneous counterpart (i.e. thSAT+abSAT: 8±3 ILCs/g of AT, P=0.002), with a difference in the proportion of the 3 subtypes of ILCs (ILC1>ILC3>ILC2). In addition, we observed an increase in EAT-ILC2 compared to other ATs and almost all these EAT-ILC2 expressed CD69 and/or CD25 activation markers (99.75±0.16%; P<0.0001). We also observed more NKs in EAT and VAT (1520±71 cells/g of AT) than in SATs (562±17 cells/g of AT); P=0.01. CONCLUSION: This is the first study to provide a comparison between innate and adaptive lymphoid cells in human epicardial versus abdominal or thoracic adipose tissues. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging. TRIAL REGISTRATION: CODECOH No. DC-2021-4518 The French agency of biomedicine PFS21-005.


Subject(s)
Adaptive Immunity , Adipose Tissue , Immunity, Innate , Pericardium , Humans , Pericardium/immunology , Pericardium/pathology , Male , Middle Aged , Female , Adipose Tissue/immunology , Aged , Adult , Lymphocytes/immunology , Intra-Abdominal Fat/immunology , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Transcriptome , Epicardial Adipose Tissue
5.
Int J Colorectal Dis ; 39(1): 84, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829434

ABSTRACT

OBJECTIVES: Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients. METHODS: A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves. RESULTS: LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator. CONCLUSION: The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.


Subject(s)
Body Composition , Colorectal Neoplasms , Lymphatic Metastasis , Neoplasm Invasiveness , ROC Curve , Humans , Male , Female , Colorectal Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Middle Aged , Aged , Neoplasm Staging , Tomography, X-Ray Computed , Risk Factors , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Adult , Retrospective Studies , Multivariate Analysis , Muscle, Skeletal/pathology , Muscle, Skeletal/diagnostic imaging , Blood Vessels/pathology , Blood Vessels/diagnostic imaging
6.
J Biol Chem ; 300(7): 107460, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38876306

ABSTRACT

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 (G6PDS188F) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PDS188F variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PDS188F 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 G6PDS188F variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.


Subject(s)
Adipocytes , Diet, High-Fat , Fatty Liver , Glucosephosphate Dehydrogenase , Hypertrophy , Obesity , Animals , Glucosephosphate Dehydrogenase/metabolism , Glucosephosphate Dehydrogenase/genetics , Male , Rats , Obesity/metabolism , Obesity/genetics , Obesity/pathology , Obesity/etiology , Diet, High-Fat/adverse effects , Adipocytes/metabolism , Adipocytes/pathology , Fatty Liver/metabolism , Fatty Liver/genetics , Fatty Liver/pathology , Liver/metabolism , Liver/pathology , Rats, Sprague-Dawley , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology
7.
Am J Pathol ; 194(8): 1494-1510, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38705384

ABSTRACT

Dyslipolysis of adipocytes plays a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, the degree of adipocyte lipolysis related to the prognoses in acute pancreatitis (AP) and the role of ATGL-mediated lipolysis in the pathogenesis of AP remain elusive. Herein, the visceral adipose tissue consumption rate in the acute stage was measured in both patients with AP and mouse models. Lipolysis levels and ATGL expression were detected in cerulein-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, atglistatin, was used in C57Bl/6N and ob/ob AP models. This study indicated that increased visceral adipose tissue consumption rate in the acute phase was independently associated with adverse prognoses in patients with AP, which was validated in mouse AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis aggravated AP. Genetic blockage of ATGL specifically in adipocytes alleviated the damage to AP. The application of atglistatin effectively protected against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.


Subject(s)
Adipocytes , Disease Models, Animal , Lipase , Lipolysis , Mice, Inbred C57BL , Pancreatitis , Animals , Lipolysis/drug effects , Lipase/metabolism , Lipase/genetics , Adipocytes/metabolism , Adipocytes/pathology , Mice , Pancreatitis/pathology , Pancreatitis/metabolism , Humans , Male , Mice, Knockout , Female , Acute Disease , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Acyltransferases
8.
Lipids Health Dis ; 23(1): 139, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741154

ABSTRACT

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.


Subject(s)
Erectile Dysfunction , ROC Curve , Male , Erectile Dysfunction/metabolism , Erectile Dysfunction/physiopathology , Humans , Middle Aged , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Biomarkers/metabolism , Adult , Homocysteine/blood , Homocysteine/metabolism , Obesity/complications , Obesity/metabolism , Aged , Risk Factors , Metabolic Syndrome/complications , Metabolic Syndrome/metabolism , Logistic Models
9.
J Diabetes ; 16(6): e13569, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38751375

ABSTRACT

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.


Subject(s)
Intra-Abdominal Fat , Muscle, Skeletal , Non-alcoholic Fatty Liver Disease , Nutrition Surveys , Humans , Intra-Abdominal Fat/pathology , Male , Cross-Sectional Studies , Female , Middle Aged , Muscle, Skeletal/pathology , Muscle, Skeletal/metabolism , Muscle, Skeletal/diagnostic imaging , Adult , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/metabolism , Sarcopenia/epidemiology , Sarcopenia/metabolism , Absorptiometry, Photon , United States/epidemiology , Aged , Risk Factors
10.
Int J Surg ; 110(7): 4221-4230, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38573065

ABSTRACT

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.


Subject(s)
Adipose Tissue , Carcinoma, Renal Cell , Kidney Neoplasms , Tomography, X-Ray Computed , Humans , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/diagnostic imaging , Kidney Neoplasms/pathology , Kidney Neoplasms/diagnostic imaging , Retrospective Studies , Male , Female , Middle Aged , Aged , Adipose Tissue/diagnostic imaging , Adipose Tissue/pathology , Neoplasm Grading , Deep Learning , Kidney/pathology , Kidney/diagnostic imaging , Algorithms , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Cohort Studies , Adult
11.
J Biol Chem ; 300(6): 107328, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679332

ABSTRACT

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.


Subject(s)
Glucose Transporter Type 4 , Insulin Resistance , Macrophages , MicroRNAs , Obesity , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Obesity/metabolism , Obesity/genetics , Obesity/pathology , Macrophages/metabolism , Mice , Glucose Transporter Type 4/metabolism , Glucose Transporter Type 4/genetics , Male , Mice, Inbred C57BL , Adipose Tissue/metabolism , Adipose Tissue/pathology , Humans , Diet, High-Fat/adverse effects , Glucose Intolerance/metabolism , Glucose Intolerance/genetics , Glucose Intolerance/pathology , Extracellular Vesicles/metabolism , Extracellular Vesicles/genetics , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology
12.
Am J Gastroenterol ; 119(6): 1117-1125, 2024 06 01.
Article in English | MEDLINE | ID: mdl-38634559

ABSTRACT

INTRODUCTION: Visceral obesity is a risk factor for reflux esophagitis (RE). We investigated the risk of RE according to visceral adipose tissue (VAT) measured by deep neural network architecture using computed tomography (CT) and evaluated the longitudinal association between abdominal adipose tissue changes and the disease course of RE. METHODS: Individuals receiving health checkups who underwent esophagogastroduodenoscopy (EGD) and abdominal CT at Seoul National University Healthcare System Gangnam Center between 2015 and 2016 were included. Visceral and subcutaneous adipose tissue areas and volumes were measured using a deep neural network architecture and CT. The association between the abdominal adipose tissue area and volume and the risk of RE was evaluated. Participants who underwent follow-up EGD and abdominal CT were selected; the effects of changes in abdominal adipose tissue area and volume on RE endoscopic grade were investigated using Cox proportional hazards regression. RESULTS: We enrolled 6,570 patients who underwent EGD and abdominal CT on the same day. RE was associated with male sex, hypertension, diabetes, excessive alcohol intake, current smoking status, and levels of physical activity. The VAT area and volume increased the risk of RE dose-dependently. A decreasing VAT volume was significantly associated with improvement in RE endoscopic grade (hazard ratio: 3.22, 95% confidence interval: 1.82-5.71). Changes in subcutaneous adipose tissue volume and the disease course of RE were not significantly correlated. DISCUSSION: Visceral obesity is strongly associated with RE. VAT volume reduction was prospectively associated with improvement in RE endoscopic grade dose-dependently. Visceral obesity is a potential target for RE treatment.


Subject(s)
Endoscopy, Digestive System , Esophagitis, Peptic , Intra-Abdominal Fat , Tomography, X-Ray Computed , Humans , Male , Female , Middle Aged , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Esophagitis, Peptic/diagnostic imaging , Esophagitis, Peptic/pathology , Endoscopy, Digestive System/methods , Risk Factors , Adult , Obesity, Abdominal/complications , Obesity, Abdominal/diagnostic imaging , Neural Networks, Computer , Aged , Retrospective Studies , Severity of Illness Index
13.
Lipids Health Dis ; 23(1): 120, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654370

ABSTRACT

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.


Subject(s)
Body Mass Index , Hyperlipidemias , Obesity, Abdominal , Pancreatitis , Severity of Illness Index , Humans , Male , Pancreatitis/diagnosis , Pancreatitis/blood , Female , Middle Aged , Adult , Obesity, Abdominal/complications , Retrospective Studies , Aged , Anthropometry/methods , Acute Disease , Intra-Abdominal Fat/pathology , Intra-Abdominal Fat/physiopathology
14.
Surg Obes Relat Dis ; 20(5): 419-424, 2024 May.
Article in English | MEDLINE | ID: mdl-38461055

ABSTRACT

BACKGROUND: Individual patterns of fat accumulation (visceral, subcutaneous, and/or liver fat) can determine cardiometabolic risk profile. OBJECTIVE: To investigate risk stratification using personalized fat z-scores in persons with a body mass index (BMI) of 30-40 kg/m2 from the UK Biobank imaging study. SETTING: Population-based study. METHODS: Whole-body magnetic resonance (MR) images of 40,174 participants from the UK Biobank imaging study were analyzed for visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) and used to calculate sex- and body size-invariant fat z-scores (VATz, aSATz, LFz). Associations between z-scores and later incident cardiovascular disease (CVD) and type 2 diabetes (T2D) were investigated using Cox proportional hazards modeling and Kaplan-Meier curves in participants with BMI 30-40 kg/m2. RESULTS: A total of 6716 participants had BMI 30-40 kg/m2 and within this group, CVD was positively associated with VATz (crude hazard ratio (cHR) [95% CI]: 1.30 [1.20-1.40], P < .001) and negatively associated with aSATz and LFz (cHR: 0.91 [0.85-0.99], P = .028, and 0.88 [0.82-0.95], P = .002). All z-scores remained significant after adjustment for sex, BMI, and age, but only VATz was significant when previous CVD was added. T2D was positively associated with VATz and LFz (cHR: 1.53 [1.40-1.67], P < .001, and 1.35 [1.23-148], P < .001) and negatively associated with aSATz (cHR: 0.90 [0.81-0.99], P = .026). All z-scores remained significant after adjustment for sex, BMI, and age. CONCLUSIONS: Personalized MR-derived fat z-scores can identify phenotypes of obesity with specific cardiometabolic risk profiles regardless of BMI. Current guidelines for bariatric surgery based on BMI exclude some of these high-risk patients.


Subject(s)
Diabetes Mellitus, Type 2 , Intra-Abdominal Fat , Magnetic Resonance Imaging , Subcutaneous Fat , Adult , Aged , Female , Humans , Male , Middle Aged , Body Mass Index , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/epidemiology , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Liver/diagnostic imaging , Liver/pathology , Obesity/complications , Risk Assessment , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology , United Kingdom/epidemiology
15.
J Endocrinol Invest ; 47(8): 1995-2005, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38308163

ABSTRACT

PURPOSE: To assess coronary inflammation by measuring the volume and density of the epicardial adipose tissue (EAT), perivascular fat attenuation index (FAI) and coronary plaque burden in patients with Cushing's syndrome (CS) based on coronary computed tomography angiography (CCTA). METHODS: This study included 29 patients with CS and 58 matched patients without CS who underwent CCTA. The EAT volume, EAT density, FAI and coronary plaque burden were measured. The high-risk plaque (HRP) was also evaluated. CS duration from diagnosis, 24-h urinary free cortisol (UFC), and abdominal visceral adipose tissue volume (VAT) of CS patients were recorded. RESULTS: The CS group had higher EAT volume (146.9 [115.4, 184.2] vs. 119.6 [69.0, 147.1] mL, P = 0.006), lower EAT density (- 78.79 ± 5.89 vs. - 75.98 ± 6.03 HU, P = 0.042), lower FAI (- 84.0 ± 8.92 vs. - 79.40 ± 10.04 HU, P = 0.038), higher total plaque volume (88.81 [36.26, 522.5] vs. 44.45 [0, 198.16] mL, P = 0.010) and more HRP plaques (7.3% vs. 1.8%, P = 0.026) than the controls. The multivariate analysis suggested that CS itself (ß [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (ß [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (ß [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (ß [95% CI] - 0.037[- 0.058, - 0.016], P = 0.001) not CS was strongly associated with EAT density. EAT volume, FAI and plaque burden increased (all P < 0.05) in 6 CS patients with follow-up CCTA. The EAT volume had a moderate correlation with abdominal VAT volume (r = 0.526, P = 0.008) in CS patients. CONCLUSIONS: Patients with CS have higher EAT volume and coronary plaque burden but less inflammation as detected by EAT density and FAI. The EAT density is associated with EAT volume but not CS itself.


Subject(s)
Adipose Tissue , Cushing Syndrome , Pericardium , Plaque, Atherosclerotic , Propensity Score , Humans , Cushing Syndrome/pathology , Female , Male , Pericardium/pathology , Pericardium/diagnostic imaging , Middle Aged , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Adipose Tissue/pathology , Adipose Tissue/diagnostic imaging , Coronary Artery Disease/pathology , Coronary Artery Disease/diagnostic imaging , Computed Tomography Angiography , Adult , Coronary Angiography , Case-Control Studies , Follow-Up Studies , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Prognosis , Epicardial Adipose Tissue
16.
Nutr Cancer ; 76(4): 316-324, 2024.
Article in English | MEDLINE | ID: mdl-38317427

ABSTRACT

Abdominal adiposity is associated with tumor development and poor clinical outcomes in breast cancer (BC) and can be identified by the measurement of waist circumference (WC) and visceral adipose tissue (VAT). This study aimed to evaluate the association between waist circumference (WC) and imaging measurement of central adiposity according to age group in women with BC. Abdominal adiposity was assessed by WC and VAT, obtained by dual-energy X-ray absorptiometry (DXA). Body mass index (BMI) was assessed. The presence of inflammation was investigated by measuring C-Reactive Protein (CRP) levels. Multivariate linear regression models were applied to verify the association between WC and VAT. The significance level adopted for all tests was 5%. This study included 112 women with a mean age of 55.5 ± 11.4 years. After adjusted models, WC remained associated with VAT and for every centimeter increase in WC, there was an increase of 3.12 cm2 (CI: 2.40 - 3.85; p < 0.001) in VAT. WC was associated with VAT in women with breast cancer, proving to be a simple, fast, and noninvasive approach that can be used as a proxy to identify visceral fat.


Subject(s)
Breast Neoplasms , Intra-Abdominal Fat , Humans , Female , Adult , Middle Aged , Aged , Waist Circumference , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Breast Neoplasms/pathology , Obesity/metabolism , Body Mass Index , Obesity, Abdominal
17.
Am J Physiol Gastrointest Liver Physiol ; 326(4): G385-G397, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38252682

ABSTRACT

A2AR-disrupted mice is characterized by severe systemic and visceral adipose tissue (VAT) inflammation. Increasing adenosine cyclase (AC), cAMP, and protein kinase A (PKA) formation through A2AR activation suppress systemic/VAT inflammation in obese mice. This study explores the effects of 4 wk A2AR agonist PSB0777 treatment on the VAT-driven pathogenic signals in hepatic and cardiac dysfunction of nonalcoholic steatohepatitis (NASH) obese mice. Among NASH mice with cardiac dysfunction, simultaneous decrease in the A2AR, AC, cAMP, and PKA levels were observed in VAT, liver, and heart. PSB0777 treatment significantly restores AC, cAMP, PKA, and hormone-sensitive lipase (HSL) levels, decreased SREBP-1/FASN, MCP-1, and CD68 levels, reduces infiltrated CD11b+ F4/80+ cells and adipogenesis in VAT of NASH + PSB0777 mice. The changes in VAT were accompanied by the suppression of hepatic and cardiac lipogenic/inflammatory/injury/apoptotic/fibrotic markers, the normalization of cardiac contractile [sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2)] marker, and cardiac dysfunction. The in vitro approach revealed that conditioned media (CM) of VAT of NASH mice (CMnash) trigger palmitic acid (PA)-like lipotoxic (lipogenic/inflammatory/apoptotic/fibrotic) effects in AML-12 and H9c2 cell systems. Significantly, A2AR agonist pretreatment-related normalization of A2AR-AC-cAMP-PKA levels was associated with the attenuation of CMnash-related upregulation of lipotoxic markers and the normalization of lipolytic (AML-12 cells) or contractile (H9C2 cells) marker/contraction. The in vivo and in vitro experiments revealed that A2AR agonists are potential agent to inhibit the effects of VAT inflammation-driven pathogenic signals on the hepatic and cardiac lipogenesis, inflammation, injury, apoptosis, fibrosis, hypocontractility, and subsequently improve hepatic and cardiac dysfunction in NASH mice.NEW & NOTEWORTHY Protective role of adenosine A2AR receptor (A2AR) and AC-cAMP-PKA signaling against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) possibly via its actions on adipocytes is well known in the past decade. Thus, this study evaluates pharmacological activities of A2AR agonist PSB0777, which has already demonstrated to treat NASH. In this study, the inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A2AR with A2AR agonist PSB0777 improves the hepatic and cardiac dysfunction of high-fat diet (HFD)-induced NASH mice.


Subject(s)
Heart Diseases , Leukemia, Myeloid, Acute , Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Intra-Abdominal Fat/pathology , Adenosine/metabolism , Mice, Obese , Liver/metabolism , Inflammation/metabolism , Fibrosis , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Mice, Inbred C57BL
18.
Int J Colorectal Dis ; 39(1): 20, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38240842

ABSTRACT

INTRODUCTION: The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant. However, its preoperative prognostic value for postoperative complications and CD relapse after ileocecal resection (ICR) remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence using magnetic resonance imaging (MRI). The primary endpoint was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis. METHODS: We conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. We included 223 patients with high-quality preoperative MRI scans, recording demographics, postoperative outcomes, and CD recurrence rates at the anastomosis. To assess adipose tissue distribution, we measured total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using MRI cross-sectional images. Ratios of these values were calculated. RESULTS: None of the radiological variables showed an association with anastomotic leakage (TFA p = 0.932, VFA p = 0.982, SFA p = 0.951, SFA/TFA p = 0.422, VFA/TFA p = 0.422), postoperative complications, or CD recurrence (TFA p = 0.264, VFA p = 0.916, SFA p = 0.103, SFA/TFA p = 0.059, VFA/TFA p = 0.059). CONCLUSIONS: Radiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Preoperative measurement of visceral fat measurement is not specific for predicting postoperative complications or CD relapse.


Subject(s)
Crohn Disease , Humans , Crohn Disease/complications , Crohn Disease/diagnostic imaging , Crohn Disease/surgery , Retrospective Studies , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Anastomotic Leak/pathology , Recurrence , Postoperative Complications/etiology , Postoperative Complications/pathology
20.
J Diabetes ; 16(1): e13472, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37749943

ABSTRACT

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 cm2 ), Group 2 (TSH level ≥4.2 µIU/mL, and VFA < 70 cm2 ), Group 3 (TSH level <4.2 µIU/mL, and VFA ≥70 cm2 ) and Group 4 (TSH level ≥4.2 µIU/mL, and VFA ≥70 cm2 ). 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.


Subject(s)
Metabolic Syndrome , Humans , Female , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Follow-Up Studies , Thyrotropin , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Postmenopause , Prospective Studies , Longitudinal Studies , Cholesterol, LDL , China/epidemiology
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