Amount Of Visceral Adipose Tissue Research Articles

Machine learning allows robust classification of visceral fat in women with obesity using common laboratory metrics

The excessive accumulation and malfunctioning of visceral adipose tissue (VAT) is a major determinant of increased risk of obesity-related comorbidities. Thus, risk stratification of people living with obesity according to their amount of VAT is of clinical interest. Currently, the most common VAT measurement methods include mathematical formulae based on anthropometric dimensions, often biased by human measurement errors, bio-impedance, and image techniques such as X-ray absorptiometry (DXA) analysis, which requires specialized equipment. However, previous studies showed the possibility of classifying people living with obesity according to their VAT through blood chemical concentrations by applying machine learning techniques. In addition, most of the efforts were spent on men living with obesity while little was done for women. Therefore, this study aims to compare the performance of the multilinear regression model (MLR) in estimating VAT and six different supervised machine learning classifiers, including logistic regression (LR), support vector machine and decision tree-based models, to categorize 149 women living with obesity. For clustering, the study population was categorized into classes 0, 1, and 2 according to their VAT and the accuracy of each MLR and classification model was evaluated using DXA-data (DXAdata), blood chemical concentrations (BLDdata), and both DXAdata and BLDdata together (ALLdata). Estimation error and R2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {R}^{2}$$\\end{document} were computed for MLR, while receiver operating characteristic (ROC) and precision-recall curves (PR) area under the curve (AUC) were used to assess the performance of every classification model. MLR models showed a poor ability to estimate VAT with mean absolute error ≥401.40\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge 401.40$$\\end{document} and R2≤0.62\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {R}^{2} \\le 0.62$$\\end{document} in all the datasets. The highest accuracy was found for LR with values of 0.57, 0.63, and 0.53 for ALLdata, DXAdata, and BLDdata, respectively. The ROC AUC showed a poor ability of both ALLdata and DXAdata to distinguish class 1 from classes 0 and 2 (AUC = 0.31, 0.71, and 0.85, respectively) as also confirmed by PR (AUC = 0.24, 0.57, and 0.73, respectively). However, improved performances were obtained when applying LR model to BLDdata (ROC AUC ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge $$\\end{document} 0.61 and PR AUC ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge $$\\end{document} 0.42), especially for class 1. These results seem to suggest that, while a direct and reliable estimation of VAT was not possible in our cohort, blood sample-derived information can robustly classify women living with obesity by machine learning-based classifiers, a fact that could benefit the clinical practice, especially in those health centres where medical imaging devices are not available. Nonetheless, these promising findings should be further validated over a larger population.

Вплив мелатоніну на розвиток ожиріння і остеопорозу

The review of modern literature presents data on the prevalence of obesity and osteoporosis in Ukraine and the world. These diseases are associated with severe and persistent symptoms, slow recovery, and a significant negative impact on patients’ quality of life. Melatonin is a hormone with enormous biological functions. As a widely available and versatile molecule in vivo, it has powerful antioxidant and anti-inflammatory properties in various bone diseases, has an effect on the restoration of damaged tissues, helps to reduce the amount of visceral adipose tissue and improves eating behavior. However, the informational analysis of the problem showed that there are still many unsolved questions regarding the optimal dosage and timing of melatonin administration, as well as the study of any possible side effects during its longterm administration. At the same time, the study of the effect of melatonin on the state of the bone system in obesity can contribute to a deeper understanding of the pathogenesis of both osteopenic and metabolic syndromes for the development of new methods of treatment and prevention.

Visceral Adipose Tissue: The Hidden Culprit for Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance in various tissues. Though conventionally associated with obesity, current research indicates that visceral adipose tissue (VAT) is the leading determining factor, wielding more influence regardless of individual body mass. The heightened metabolic activity of VAT encourages the circulation of free fatty acid (FFA) molecules, which induce insulin resistance in surrounding tissues. Individuals most vulnerable to this preferential fat deposition are older males with ancestral ties to Asian countries because genetics and sex hormones are pivotal factors for VAT accumulation. However, interventions in one's diet and lifestyle have the potential to strategically discourage the growth of VAT. This illuminates the possibility that the expansion of VAT and, subsequently, the risk of T2D development are preventable. Therefore, by reducing the amount of VAT accumulated in an individual and preventing it from building up, one can effectively control and prevent the development of T2D.

Moderate Intra-Abdominal Pressure Levels in Robot-Assisted Radical Prostatectomy Seem to Have No Negative Impact on Clinical Outcomes.

Introduction: Radical prostatectomy is increasingly performed laparoscopically with robot assistance (RALRP). RALRP, as with all laparoscopic procedures, requires a pneumoperitoneum, which might result in peritoneal inflammatory response reactions and postoperative pain. The aim of this retrospective single-centre study was to analyse the effects of a pneumoperitoneum during RARLP on clinical outcomes. Methods: All patients who underwent robot-guided prostatectomy in our clinic were included, with the exception of patients who were converted to open prostatectomy. C-reactive protein was used as a marker for the primary outcome, namely the postoperative inflammatory response. Intra-abdominal pressure (IAP) was evaluated as a potential factor influencing inflammation. In addition, the waist-hip ratio was used to estimate the amount of visceral adipose tissue, and the administration of dexamethasone was considered as a factor influencing inflammation. The Visual Analogue Scale (VAS) was used to determine postoperative pain. Patients were consecutively recruited between 1 September 2020 and 31 March 2022. Results: A total of 135 consecutive patients were included. The median waist-hip ratio was 0.55. The median duration of the pneumoperitoneum was 143 min. The median values of the average and maximum IAP values were 10 mmHg and 15 mmHg, respectively. The mean CRP of the first postoperative day was 6.2 mg/dL. The median VAS pain level decreased from 2 to 1 from the first to the third postoperative day. On the first postoperative day, 16 patients complained of shoulder pain. In addition, 134 patients were given some form of opioid pain treatment following surgery. Conclusion: We could not identify any relevant associations between the duration and IAP of the pneumoperitoneum and the indirect markers of inflammation or indicators of pain, or between the latter and the amount of visceral adipose tissue. In addition, we found no significant effect of the administration of dexamethasone on postoperative inflammation. The results point to a noninferior tolerability of moderate pressure during the procedure compared to the commonly utilised higher pressure, yet this must be confirmed in randomised controlled trials.

Subcutaneous and Visceral Fat: Relation with Brown Adipose Tissue Activation in Women.

Brown adipose tissue (BAT) helps control body weight and is inversely correlated with body fat, but it is unclear whether it is subcutaneous adipose tissue (SAT) or visceral adipose tissue (VAT) that is related to BAT activation. The presented study aimed to verify the relation of SAT and VAT on BAT activation through infrared thermography (IRT) and cold stimulation in adult women. Forty women were evaluated in body composition and skin temperature (Tskin) acquisition by IRT. Student's independent t-test, Pearson's correlation, and two-way repeated measures ANOVA with Tukey post-hoc were applied. Women with low amounts of SAT and VAT had a significant increase in supraclavicular Tskin (SCVT). Medium negative degrees of linear variation were found before and after cold stimulation between SCVT, SAT and VAT. A significant effect of the moment factor and the group factor on the SCVT between subjects divided into the groups were pointed out. No difference was found in the relation between SAT, VAT, and BAT in adult women, pointing out that both types of fat are equally related. These results can help clinical practice understand clearly, through IRT, that the high accumulation of SAT and VAT can impair the activation of BAT and hinder the loss of weight in women.

Distinct Temporal Dynamic Serum Metabolite Profiles Characterize Treatment Response and Early Toxicity after B-Cell Lymphoma Directed CAR-T-Cell Therapy

Introduction: CD19 chimeric antigen receptor T-cell therapy (CD19.CAR-T) has profoundly improved treatment options for patients with relapsed/refractory B-cell lymphomas (r/r BCL), but is also associated with distinct toxicities. To elucidate host-intrinsic immunometabolic factors contributing to clinical benefit or immunotoxicity, we recently demonstrated that an increase of metabolically high-risk adipose tissue mass is associated with an elevated cytokine release syndrome (CRS) risk but also with improved survival (Haematologica 2022, CIR 2023). To gain further insights into the underlying immunometabolic mechanisms, we analyzed temporal dynamic changes of serum metabolites in r/r BCL patients during the first 14 days of CD19.CAR-T treatment. Methods: In this single-center analysis, we studied patients receiving CD19.CAR-T for r/r large BCL or mantle cell lymphoma (MCL) between 01/2019 and 12/2021 in a real-world setting. All patients were consecutively treated in our department (LMU University Hospital) and serum was prospectively collected in the morning hours from fasted patients beginning at the day of CAR-T infusion (D0), and 3-5 and 14 days later. Using liquid chromatography mass-spectrometry, we quantitatively analyzed a total of 305 water-soluble metabolites and 734 lipids. Metabolomic data was integrated with clinical patient records including CRS, 1-year progression-free survial (PFS) and amount of visceral adipose tissue (VAT). Results: In total, we measured 170 serum samples from 55 r/r LBCL and 4 r/r MCL patients, of which 52 had serial samples at all three time points (D0: 55, D3-5: 59, D14: 56). The following CAR-T products were administered: axi-cel (n = 26), tisa-cel (n = 29) and brexu-cel (n = 4). 25 (42.4%) patients developed a CRS grade ≥ 2, while 34 patients had a CRS grade 0-1. The best 90-day overall response rate was 52.5%, with a complete remission rate of 42.4%. At 1 year, 67.8% of patients progressed. From the 1039 metabolites measured, 525 metabolites passed quality control. Metabolite values were normalized and auto-scaled for further analysis. A partial least square differential analysis based on the collected time points led to a clear separation of samples with uric acid, desoxy-ribose-5-phosphate (dRibose-P), essential amino acids and (phospho)lipids having the strongest impact. Whereas 56 metabolites showed a significant increase from D0 to D14 led by uric and essential amino acids, 34 metabolites decreased over the course of treatment with the strongest reduction in dRibose-P and sphingosine phosphate. Performing a metabolic pathway enrichment analysis based on the most altered metabolite levels, we detected 22 significantly affected metabolic pathways and programs including aerobic glycolysis, urea cycle, amino acid and lipid metabolism (FDR < 0.1, Fig. 1A). To further delineate metabolite changes in regards to CRS, 1-year PFS and amount of VAT, we conducted a multivariate empirical bayes analysis of variance to specifically detect metabolites with differential temporal dynamics and considered all metabolites with an FDR < 0.1. Patients who developed a CRS ≥ 2° showed increased levels of kynurenine, phosphatidylethanolamides and lysophosphatidylserines, and decreased levels of ornithine and phosphatidylinositols. 1-year progressors showed a significant increase of several phosphatidylinositols beginning at D3-5 after CAR-T infusion, and decreased levels of phosphatidylcholines. For VAT, we used a threshold of 144 cm² which was derived from previously conducted computer tomography segmentation analyses. As expected, VAT cohorts mostly differed in fatty acid metabolism-associated metabolites including (acyl)carnitines, cholesterol esters, triglycerides and xanthine. In order to identify metabolites being associated with multiple outcomes, we looked for mutual metabolites among distinct cohort profiles. Here, one example is phosphatidylinositol-(22:5/16:0), which was increased in CRS 0-1° and 1y-progressors ( Fig. 1B). Conclusions: Our study highlights that CD19.CAR-T treatment is accompanied by broad changes in the serum metabolome of r/r BCL patients, which can be used to profile patients being affected by CAR-T-related immunotoxicity and their response to treatment. In ongoing analyses, we evaluate the use of these profiles for predictive models, and assess their impact on CAR-T cell function in-vitro.

Visceral adipose tissue and risk of nonalcoholic fatty liver disease: A Mendelian randomization study.

Observational studies have shown that visceral adipose tissue (VAT) can increase the risk of nonalcoholic fatty liver disease (NAFLD). However, the causality of this association remains unclear. Therefore, this study aimed to explore the causal association between VAT and NAFLD. We obtained single-nucleotide polymorphisms strongly associated with VAT (n = 325,153) from large-scale genome-wide association studies. Summary-level data for NAFLD (2275 cases and 375,002 controls) was available from the FinnGen consortium. We applied two-sample Mendelian randomization (MR) to determine the causal association between VAT and NAFLD. The random-effects inverse-variance weighted (IVW) method was used as the main MR approach, with alternate methods including the weighted median (WM) approach and MR-Egger regression. In addition, we conducted sensitivity analyses to assess the robustness of MR analyses. Genetically predicted higher VAT mass is causally associated with a higher risk of NAFLD. The three analysis results of MR were as follows: IVW (β = 0.665, odds ratio [OR] = 1.944, 95% confidence interval [CI] = 1.482-2.550, p = 1.58e-06], WM (β = 0.615, OR = 1.849, 95% CI = 1.272-2.689, p = 1.29e-03), and MR-Egger (β = 1.250, OR = 3.490, 95% CI = 1.522-7.998, p = 3.52e-03). In the sensitivity analysis, the data showed heterogeneity (p < 0.05) but no pleiotropy (p = 0.145). This study provided genetic evidence that higher VAT mass causally associated with a higher risk of NAFLD. The amount of VAT could be reduced using a therapeutic strategy for managing NAFLD.

Correlation analysis of the abdominal visceral fat area with the structure and function of the heart and liver in obesity: a prospective magnetic resonance imaging study

BackgroundThe differences in fat deposition sites exhibit varying degrees of systemic inflammatory responses and organ damage, especially in obese individuals with excessive visceral fat. Visceral fat, which is closely related to an increase in mortality rates related to heart and liver diseases. However, few studies have analysed the differences in heart and liver indicators and their correlation among groups based on the abdominal visceral fat area (AVFA).ObjectiveClarifying the differences in and correlations of heart and liver indicators among groups with different severities of AVFA by magnetic resonance imaging (MRI).MethodsSixty-nine subjects with obesity were enrolled. The study group consisted of forty-one individuals (AVFA ≥ 150 cm2), and the control group consisted of twenty-eight individuals (100 cm2 ≤ AVFA < 150 cm2). The differences in and correlations between clinical, laboratory, and MRI indicators of the heart and liver between the two groups were analysed.ResultsIn the study group, the incidences of type 2 diabetes mellitus (T2DM) and insulin resistance were higher, and liver function indicators were worse. The left ventricular eccentricity ratio (LVER), left ventricular mass (LVM) and global peak wall thickness (GPWT) were higher in the study group than in the control group (P = 0.002, P = 0.001, P = 0.03), and the left ventricle global longitudinal strain (LVGLS) was lower in the study group than in the control group (P = 0.016). The pericardiac adipose tissue volume (PATV) and myocardial proton density fat fraction (M-PDFF) were higher in the study group than in the control group (P = 0.001, P = 0.001). The hepatic proton density fat fraction (H-PDFF) and abdominal subcutaneous fat area (ASFA) were higher in the study group than in the control group (P < 0.001, P = 0.012). There was a moderate positive correlation (ρ = 0.39–0.59, P < 0.001) between the AVFA and LVER, LVM, GPWT, LVGLS, and H-PDFF. There was no difference in right ventricular and most left ventricular systolic and diastolic function between the two groups.ConclusionThe high AVFA group had a larger LVM, GPWT and PATV, more obvious changes in LVER, impaired left ventricular diastolic function, an increased risk of heart disease, and more severe hepatic fat deposition and liver injury. Therefore, there is a correlation between the amount of visceral adipose tissue and subclinical cardiac changes and liver injury.

Is there a role for conicity index in 10-year risk cardiovascular disease prediction?

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease (CVD) is the leading cause of death globally and one of the most frequent causes of disability. Therefore, the complete and correct evaluation of cardiovascular risk factors is essential to timely prevent CVD. Once central obesity is related with the amount of visceral adipose tissue - an independent predictor of CVD risk - its assessment may play an important role in 10-year CVD prediction. The conicity index (C-Index) assesses central adiposity but there is limited data regarding its role in 10-year CVD risk prediction. Purpose To evaluate the role of C-Index in predicting 10-year risk of fatal and non-fatal CVD according to SCORE2 and SCORE2-OP models in a moderate-risk country population. Methods We conducted a cross-sectional study in a Portuguese population sample. Individuals aged 40-90 years without known established Atherosclerotic Cardiovascular Disease, Diabetes mellitus, Chronic Kidney Disease or Familial Hypercholesterolemia were included in the study through a local cardiovascular (CV) screening event in Portugal, during May 2022. The C-Index was calculated for each individual according to the Valdez’s formula. For CVD risk assessment, we used the cut-offs values proposed by Pitanga et al. 1.18 for women and 1.25 for men. The population was divided into two groups according to the C-Index (risk high versus low). The 10-year risk of fatal and non-fatal CVD was calculated using SCORE2 and SCORE2-OP models. Results A total of 431 individuals were enrolled in this study. Median age was 71 years (Q1-Q3: 65-75) and 66.8% of were women. A total of 48.1% had hypertension, 38.3% dyslipidemia, 25.5% obesity and 6.6% were active smokers. Overall, 387 (90.2%) individuals were found to have elevated C-Index (SCORE2/2-OP mean± DP: 14.99± 7.56 versus 09.81± 3.37), of which 259 were female. In the univariate analysis, there was a correlation between C-Index and estimation of the Risk Cardiovascular Disease according to SCORE2/2-OP but was not statistically significant (Exp (beta) 95 % (CI):2.52 (-2.06-7.10, p=0.28)). However, in the multivariable linear regression analyzes the variable waist circumference (Exp (beta) 95 % (CI)18.47 (4.69 – 32.24, p&amp;lt;0.001)) was independent predictive factor related to the Risk of Cardiovascular Disease according to SCORE2 and SCORE2-OP. Conclusions In the present study most of the patients were categorized into high-risk category. Conicity index was not significantly correlated with estimation of the Risk of Cardiovascular Disease according to SCORE2 and SCORE2-OP models, but the variable waist circumference (Exp (beta) 95 % (CI)18.47 (4.69 – 32.24, p&amp;lt;0.001)) was an independent predictive factor related. More studies are needed to assess the role of C-Index in CVD risk prediction.

Visceral obesity measured using computed tomography scans: No significant association with mortality in critically ill patients

IntroductionThe association between obesity and outcome in critical illness is unclear. Since the amount of visceral adipose tissue(VAT) rather than BMI mediates the health effects of obesity we aimed to investigate the association between visceral obesity, BMI and 90-day mortality in critically ill patients. MethodIn 555 critically ill patients (68% male), the VAT Index(VATI) was measured using Computed Tomography scans on the level of vertebra L3. The association between visceral obesity, BMI and 90-day mortality was investigated using univariable and multivariable analyses, correcting for age, sex, APACHE II score, sarcopenia and muscle quality. ResultsVisceral obesity was present in 48.1% of the patients and its prevalence was similar in males and females. Mortality was similar amongst patients with and without visceral obesity (27.7% vs 24.0%, p = 0.31). The corrected odds ratio of 90-day mortality for visceral obesity was 0.667 (95%CI 0.424–1.049, p = 0.080). Using normal BMI as reference, the corrected odds ratio for overweight was 0.721 (95%CI 0.447–1.164 p = 0.181) and for obesity 0.462 (95%CI 0.208–1.027, p = 0.058). ConclusionNo significant association of visceral obesity and BMI with 90-day mortality was observed in critically ill patients, although obesity and visceral obesity tended to be associated with improved 90-day mortality.

A Low Daily Intake of Simple Sugars in the Diet Is Associated with Improved Liver Function in Cirrhotic Liver Transplant Candidates.

(1) Background: We investigated, for the first time, whether dietary simple sugar intake affects MELD score changes over time in a cohort of cirrhotic liver transplant candidates. (2) Methods: the MELD score, dietary habits using a 3-day food diary, and visceral adipose tissue index (VATI) measured with CT scan were assessed in 80 consecutive outpatient cirrhotic patients at baseline, after counseling to follow current nutritional guidelines. The MELD score was reassessed after six months and the DELTA-MELD was calculated as the MELD at the second assessment minus the MELD at baseline. (3) Results: Compared with the baseline, the MELD score of cirrhotic patients at the end of the study was decreased, stable, or increased in 36%, 8% and 56% of patients, respectively. In separate multiple linear regression models, DELTA-MELD was positively and independently correlated with the daily intake of simple sugars expressed in g/kg body weight (p = 0.01) or as a percentage of total caloric intake (p = 0.0004) and with the number of daily portions of fruit, added sugar, jam, and honey (p = 0.003). These associations were present almost exclusively in patients with VATI above the median value. (4) Conclusions: In cirrhotic patients with high amounts of visceral adipose tissue the consumption of simple sugars and fructose should be limited to improve their clinical outcome.

IMPACTS OF EXERCISE TRAINING ON THE VISCERAL ADIPOSE TISSUE AMONG INDIVIDUALS WITH NORMAL BODY MASS INDEX: A SYSTEMATIC REVIEW

https://youtu.be/617rv0W_7Kc BACKGROUND The thin outside fat inside (TOFI) phenotype, an obesity expression, is recognized by a high amount of visceral adipose tissue (VAT) despite average anthropometric measurements such as normal body mass index (BMI). High VAT is a considerable risk of metabolic syndrome. As a beneficial intervention, exercise training can decrease body fat amount. This review aimed to investigate exercise efficiency on VAT in individuals with normal BMI. METHODS Electronic databases were used to detect studies related to exercise training intervention on VAT in normal BMI individuals from 1999 to 2022. Inclusion criteria included acute, four weeks or more; duration intervention of aerobic training (AT), resistance training (RT) or combination training (COM) with adults. Participants BMIs were approximately 26 kg/m2 or less in studies investigating VAT differences between sedentary and active individuals. Acceptable body assessment measurements in the studies used computed tomography, magnetic resonance imaging, or dual-energy x-ray absorptiometry. RESULTS The primary search resulted in 217 original studies and 11 were included. The most common intervention was AT, using treadmill running, and the most common mode of RT was weight machines. Frequency of training averaged 3 days per week of 30- to- 90 minute sessions. AT intensity was demonstrated with the percentage of maximum oxygen consumption (VO2 max), peak rate of oxygen consumption (VO2peak), heart rate reserve (HRR), or maximal heart rate (MHR) in the range of 55% to 120%. The most common range was 60–70% MHR. The intensity of RT was determined as one-repetition maximum (1-RM), ranging between 60–80% 1RM. One study used interval modality intervention. Seven studies show a significant decrease in VAT values. The most impactful training was AT with two studies using COM also reported benefits. The most common unit of measurement used for VAT was cm2. Other studies used varying units such as 1) kg, 2) cm3, 3) liter, and 4) percentage of total body fat. The range of significant change in VAT scores was −2.5 ± 7.2 cm2 to −19.3 ± 12.7 cm2. Additionally, one study reported significant differences in VAT observed between active and sedentary individuals and one study reported no demonstrated differences using RT. CONCLUSIONS The systematic review suggests exercise training could be a beneficial intervention for improved VAT changes. However, exercise modality should be taken into account alongside acute variables such as volume, intensity, duration, and frequency. Based on findings, AT is the most effective modality and RT as another exercise option needs more investigation.

Relationship Between Visceral Adipose Tissue and Bone Mineral Density in Older People: Results from AHAP Study

Introduction: Due to discrepancy of the relationship between visceral adipose tissue (VAT) and bone mineral density (BMD), this study was performed to determine the relationship between BMD and VAT in the elderly. Methodology: This cross-sectional study is part of the second wave of Amirkola Health and Ageing Project (AHAP), including 1,200 people aged 60 years and older. BMD and VAT were measured by dual-energy X-ray absorptiometry (DXA) in Hologic equipment. Based on the amount of VAT, individuals were divided into four quartiles. Then, the data were statistically analyzed by SPSS22 software using chi-square, ANOVA, Pearson correlation coefficient and logistic regression. Results: The mean age of the participants was 69.6 ± 6.9 year and the mean VAT was 862.6 ± 337.8 gram. In this study, people with osteoporosis had less VAT (p<0.0001). Furthermore, with the increase in the amount of VAT, BMD increased in the femoral region and lumbar spine (p<0.0001). There was a positive and significant correlation between VAT and BMD in the femoral region (r = 0.267) and lumbar spine (r = 0.197) (p<0.0001). After performing multiple logistic regression analysis in the presence of factors such as age, gender, body mass index and especially lean mass, the protective role of VAT against osteoporosis was maintained (OR=0.510, CI95% (0.290-0.895)) (P = 0.019). Conclusions: This study has shown that VAT can independently have a positive association with BMD in the elderly.

High visceral adipose tissue area is independently associated with early allograft dysfunction in liver transplantation recipients: a propensity score analysis

ObjectivesTo evaluate the association between adipose tissue distribution and early allograft dysfunction (EAD) in liver transplantation (LT) recipients.MethodsA total of 175 patients who received LT from April 2015 to September 2020 were enrolled in this retrospective study. The areas of abdominal adipose tissue and skeletal muscle of all patients were measured based on the preoperative CT images. The appropriate statistical methods including the propensity score-matched (PSM) analysis were performed to identify the association between adipose tissue distribution and EAD.ResultsOf 175 LT recipients, 55 patients (31.4%) finally developed EAD. The multivariate logistic analysis revealed that preoperative serum albumin (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17–0.70), platelet–lymphocyte ratio (OR 2.35, 95% CI 1.18–4.79), and visceral adipose tissue (VAT) area (OR 3.17, 95% CI 1.56–6.43) were independent associated with EAD. After PSM analysis, VAT area was still significantly associated with EAD (OR 3.95, 95% CI 1.16–13.51). In survival analysis, no significant difference was identified in one-year graft failure (log-rank: p = 0.487), and conversely result was identified in overall survival (OS) (log-rank: p = 0.012; hazard ratio (HR) 4.10, 95% CI 1.27–13.16).ConclusionsLT recipients with high VAT area have higher risk for the occurrence of EAD, and high VAT area might have certain clinical value for predicting the poor OS of patients. For LT candidates with large amount of VAT, the clinicians can take clinical interventions by suggesting physical and nutritional treatments to improve outcomes after LT.

Quantity of adipose tissue and adipose tissue dysfunction and the risk of cancer in individuals at high risk of cardiovascular disease

Abstract Background Individuals with cardiovascular disease (CVD) are at increased risk of cancer compared to the general population. Adipose tissue dysfunction, as a consequence of excess adipose tissue, contributes to this risk via production of several hormones and cytokines. Whether the high risk of cancer in people with type 2 diabetes (T2D) is mainly attributable to the quantity of adipose tissue or the degree of adipose tissue dysfunction, is unknown. Purpose To assess the relation between the quantity of adipose tissue and adipose tissue dysfunction and the risk of cancer in a cohort of patients at high risk of CVD, with and without T2D. Methods 10792 participants from the UCC-SMART study were included for this prospective cohort study, including 7026 individuals with a history of CVD and 1769 individuals with pre-existent T2D. The effect of quantitative measures of adiposity [BMI, waist circumference and ultrasonographically determined visceral adipose tissue (VAT)] and of the degree of adipose tissue dysfunction on the risk of cancer was assessed using Cox proportional hazards models adjusted for confounders. Adipose tissue dysfunction was quantified by metabolic dysfunction (modified metabolic syndrome criteria with waist circumference replaced by hsCRP), the estimated glucose disposal rate (eGDR, a measure of insulin resistance), and HOMA-IR (only in people without T2D). Potential effect modification by T2D was tested by adding an interaction term to the models. Results During a median of 8.6 (IQR 5.0–12.8) years of follow-up, 1164 individuals were diagnosed with cancer, of which 219 individuals had pre-existent T2D. Incidence rates were 14.0 and 11.6 per 1000 person-years for people with and without T2D, respectively. Increases per SD in BMI [HR 0.98 (95% CI 0.92–1.05)], waist circumference [HR 1.01 (95% CI 0.95–1.09)] and VAT [HR 1.03 (95% CI 0.97–1.10)] were not significantly associated with an increased risk of cancer. These relations were not different for people with and without T2D (p&amp;gt;0.05). Metabolic dysfunction was associated with a higher risk of cancer [4–5 vs. 0–1 components: HR 1.14 (95% CI 1.03–1.25)]. The relation between eGDR and incident malignancy was different for people without T2D [HR 0.97 (95% CI 0.93–1.01)] than for people with T2D [HR 1.06 (95% CI 0.97–1.16)] (p=0.04), with this last relation being more pronounced in people with a higher amount of VAT. No significant relation was observed between HOMA-IR and the risk of cancer in people without T2D [HR 0.99 (95% CI 0.96–1.02)]. Conclusion Adipose tissue dysfunction, assessed by the degree of metabolic dysfunction, is associated with a higher risk of cancer in people at high risk of CVD. No significant associations were observed for quantitative measures of adiposity. The higher risk of cancer among individuals with adipose tissue dysfunction warrants awareness among clinicians and emphasizes the importance of obesity prevention. Funding Acknowledgement Type of funding sources: None.

Clinicopathological and Body Composition Analysis of VHL and TTN Gene Mutations in Clear Cell Renal Cell Carcinoma: An Exploratory Study

Background: The Cancer Genome Atlas (TCGA) Research Network revealed numerous clear cell renal cell carcinoma (ccRCC) gene mutations among which titin (TTN). The link between excessive amounts of visceral adipose tissue (VAT) and ccRCC pathogenesis is known. A relationship between VHL and TTN gene mutations and a CT-derived estimation of body composition in ccRCC patients has been evaluated. Methods: We retrospectively assessed patients from the TCGA-kidney renal clear cell carcinoma (KIRC) database for evaluation of clinicopathological and body composition analysis of ccRCC VHL and TTN gene mutations. Results: Gene expression levels and survival were assessed on a large cohort of 483 patients and 533 tumor samples. A statistically significant difference of VHL expression reduction in primary tumor (p &lt; 0.0001) and a TTN expression increase in primary tumor (p &lt; 0.0001) was shown. TTN high expression levels was associated with statistically significant lower KIRC patient survival at eight years (p &lt; 0.05). For body composition analysis, we included 54 male patients divided into two groups: ccRCC-VHL (n = 41) and ccRCC-TTN (n = 13) groups. Statistically significant differences between the two groups were obtained for total adipose tissue (TAT) (p &lt; 0.01), VAT (p &lt; 0.05), subcutaneous adipose tissue (SAT) (p &lt; 0.05) and total abdominal muscle (TAM) (p &lt; 0.05) areas. Conclusion: This study demonstrates a link between ccRCC TTN gene mutation and shorter patient survival. The reduction of the analyzed tissues might be a risk of cancer cachexia in ccRCC patients with TTN gene mutation.

BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH

The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets.

Significant Decrease in Glycated Hemoglobin, 2h-Post-Load Glucose and High-Sensitivity C-Reactive Protein Levels in Patients with Abnormal Body Mass Index after Therapy with Manual Lymphatic Drainage.

The objective of this study was to investigate the effect of manual lymphatic drainage (MLD) on the insulin resistance parameter (HOMA-IR), glycated hemoglobin (HbA1c), C-peptide, insulin, fasting plasma glucose (FPG), 2h-post-loadglucose (2h-PG) and the concentration of high-sensitivity C-reactive protein (hsCRP) in patients with abnormal body mass index. The study involved 30 patients, including patients with normal body weight (as a control group; group I; n = 14), overweight patients (group II; n = 9) and obese patients (group III; n = 7). Each patient underwent 10 sessions of MLD therapy, 3 times a week for 30 min. In addition, we measured body mass index (BMI) and waist-to-hip ratio (WHR) and performed body composition analysis as well as biochemical tests before MLD therapy (stage 0′) and after MLD therapy (stage 1′). A statistically significant correlation was demonstrated between the concentration of C-peptide, BMI, the amount of visceral adipose tissue (r = 0.87, p = 0.003; r = 0.76, p = 0.003, respectively), and the HOMA-IR index, BMI and the amount of visceral adipose tissue (r = 0.86, p = 0.005; r = 0.84, p = 0.042, respectively), before and after MLD therapy. In overweight patients (group II), a statistically significant (p = 0.041) decrease in the hsCRP level by 2.9 mg/L and a significant (p = 0.050) decrease in the 2h-PG level by 12 mg/dL after the MLD therapy was detected. Moreover, in the group of obese patients (group III), a statistically significant (p = 0.013) decrease in HbA1c level by 0.2% after MLD therapy was demonstrated. Our results indicate that MLD may have a positive effect on selected biochemical parameters, with the most favorable changes in overweight patients. Further studies in a larger number of patients are warranted to confirm our findings, to test in-depth their mechanism, and to investigate clinical benefits of this alternative therapy in patients with abnormal body mass index.

Associations of visceral adipose tissue with bone mineral density and fracture: observational and Mendelian randomization studies

BackgroundThe associations between visceral adipose tissue (VAT) and bone mineral density (BMD) or fracture have been controversial and the causality of the associations remains to be assessed. This study aimed to explore the associations of VAT^ (predicted value of VAT mass) with BMD and fracture risk in men and women, and to examine their potential causation by two-sample Mendelian randomization (MR) analyses.MethodsUK Biobank is a large, population-based prospective cohort study that recruited more than 500,000 participants aged 40–69 in the United Kingdom from 2006 to 2010. In this study, we used a validated and reliable prediction model to estimate the VAT amount of the participants. On this basis, linear and nonlinear multivariable statistical models were used to explore the association of VAT^ with BMD and fracture risk in different groups of sex and BMI. In observational analyses, the multivariable linear regression model and Cox proportional-hazards model were used to assess VAT^ association with BMD and fracture risk, respectively. Inverse variance weighting was used as the main result of MR analysis.ResultsIn 190,836 men, an inverted U-shaped association was observed between VAT^ and heel BMD (P for nonlinearity < 0.001), with a turning point of VAT^ = 1.25 kg. Per kg increase in VAT^ was associated with a 0.13 standard deviation (SD) increase in heel BMD (P = 1.5 × 10−16) among men with lower amounts of VAT^, and associated with a 0.05 SD decrease in heel BMD (P = 1.3 × 10−15) among men with higher amounts of VAT^. In 193,592 women, per kg increase in VAT^ was monotonically associated with a 0.16 SD increase in heel BMD (P = 1.2 × 10−136, P for VAT^-sex interaction = 8.4 × 10−51). During a median follow-up of 8.2 years, VAT^ was associated with lower risks of hip fractures in the overall men and women (P for VAT^-sex interaction = 1.9 × 10−4 for total fractures; 1.5 × 10−4 for other fractures). There were significant interactions of VAT^ and BMI on heel BMD and fracture risks in men only (P for VAT^-BMI interaction = 5.9 × 10−31 for heel BMD; 2.7 × 10−4 for total fractures; 5.7 × 10−3 for hip fractures; 6.8 × 10−3 for other fractures). In two-sample MR analyses, evidence of causality was not observed between VAT^ and DXA-derived BMD or fractures.ConclusionsThese novel findings demonstrated gender-dependent associations of VAT^ with BMD and fracture risk, with the association in men being modified by adiposity. Evidence of causality was not observed, suggesting that the observational association of VAT^ with BMD and fracture risk could be the result of confounding.

A Reliable Estimate of Visceral Fat Area From Simple Anthropometric Measurements in Chinese Overweight and Obese Individuals.

ObjectiveVisceral obesity, reflected by the amount of visceral adipose tissue (VAT), is associated with multiple chronic diseases and metabolic disorders. The visceral fat area (VFA), measured by MRI, is the ‘gold standard’ for diagnosis of visceral obesity. In this study, a simple model to predict VFA was constructed to facilitate the identification and monitoring of patients who are at high risk of visceral obesity.MethodsThe 721 overweight and obese participants were divided into two groups according to sex, then randomly assigned to derivation and validation cohorts in a 1:2 ratio. Data from the derivation group were used to construct a multiple linear regression model; data from the validation group were used to verify the validity of the model.ResultsThe following prediction equations, applicable to both sexes, were developed based on age, waist circumference (WC) and neck circumference (NC) that exhibited strong correlations with the VFA: VFA=3.7×age+2.4×WC+5.5×NC-443.6 (R2 = 0.511, adjusted R2 = 0.481, for men) and VFA=2.8×age+1.7×WC+6.5×NC-367.3 (R2 = 0.442, adjusted R2 = 0.433, for women). The data demonstrated good fit for both sexes. A comparison of the predicted and actual VFA in the verification group confirmed the accuracy of the equations: for men, R2 = 0.489, adjusted R2 = 0.484 and intra-class correlation coefficient (ICC) = 0.653 (p < 0.001) and for women: R2 = 0.538, adjusted R2= 0.536 and ICC = 0.672 (p < 0.001). The actual and predicted VFAs also showed good agreement in a Bland-Altman plot, indicating the significant correlations of both equations with the actual VFA.ConclusionsBased on readily available anthropometric data, VFA prediction equations consisting of age, WC and NC were developed. The equations are robust, with good predictive power in both sexes; they provide ideal tools for the early detection of visceral obesity in Chinese overweight and obese individuals.