Visceral Adipose Tissue Volume Research Articles

MRI adipose tissue segmentation and quantification in R (RAdipoSeg)

BackgroundExcess adipose tissue is associated with increased cardiovascular and metabolic risk, but the volume of visceral and subcutaneous adipose tissue poses different metabolic risks. MRI with fat suppression can be used to accurately quantify adipose depots. We have developed a new semi-automatic method, RAdipoSeg, for MRI adipose tissue segmentation and quantification in the free and open source statistical software R.MethodsMRI images were obtained from wild-type mice on high- or low-fat diet, and from 20 human subjects without clinical signs of metabolic dysfunction. For each mouse and human subject, respectively, 10 images were segmented with RAdipoSeg and with the commercially available software SliceOmatic. Jaccard difference, relative volume difference and Spearman’s rank correlation coefficients were calculated for each group. Agreement between the two methods were analysed with Bland–Altman plots.ResultsRAdipoSeg performed similarly to the commercial software. The mean Jaccard differences were 10–29% and the relative volume differences were below ( ±) 20%. Spearman’s rank correlation coefficient gave p-values below 0.05 for both mouse and human images. The Bland–Altman plots indicated some systematic and proporitional bias, which can be countered by the flexible nature of the method.ConclusionRAdipoSeg is a reliable and low cost method for fat segmentation in studies of mice and humans.

Age at Menarche Mediating Visceral Adipose Tissue's Influence on Pre-eclampsia: A Mendelian Randomization Study.

The association between visceral adipose tissue (VAT) and pre-eclampsia (PE) shows inconsistent results and the underlying mediator remains unknown. We aimed to explore the causal effect of VAT on PE risks and the mediation role of age at menarche (AAM) in explaining this relationship. Summary data for PE were obtained from the FinnGen genome-wide association study (3556 cases and 114 735 controls). For exposure data, 70 genetic variants associated with the predicted VAT in 161 149 European women from UK Biobank were used as instrumental variables. Inverse variance weighted and multiple sensitivity analyses were applied. We also conducted multivariable Mendelian randomization (MR) analyses to test the association between VAT-associated single-nucleotide variations and PE. Next, mediation analyses were performed to study whether the association between VAT and PE was mediated via AAM. In univariable MR analysis, higher volume of VAT was associated with the advancement of AAM and increased PE risk (beta = -0.33; 95% CI, -0.49 to -0.16 for AAM; odds ratio 1.65, 95% CI, 1.23 to 2.20 for PE). After adjusting for waist circumference, waist to hip ratio, and hip circumference, the multivariable MR results presented the consistent positive causality of VAT on PE. Two-step MR analysis proved an estimated 14.3% of the positive effect of VAT on PE was mediated by AAM. Our findings provided evidence of the causal relationship between VAT and PE and proved VAT could accelerate AAM and then contribute to the risk of incident PE.

Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events

IntroductionDuodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycaemia and metabolic health in patients with type 2 diabetes mellitus (T2DM). DMR has an insulin sensitizing effect in patients with T2DM. Reducing hyperinsulinemia can improve cardiovascular health. In the INSPIRE trial, we combined a single DMR with a glucagon-like-peptide-1 receptor agonist (GLP-1RA) and demonstrated elimination of insulin treatment in 69% of patients at 6 months and 53% of patients at 18 months while improving glycaemic control and metabolic health. We hypothesized that this treatment approach is associated with improved cardiovascular health, by reducing hyperinsulinemia.MethodsBefore and 6 months after starting the combination treatment to replace insulin, the following assessments were performed to evaluate cardiovascular health: magnetic resonance imaging (MRI) to measure abdominal visceral adipose tissue volume, ambulatory 24 h blood pressure (ABPM) analysis, postprandial insulin and triglycerides, fasting lipid panel and urine microalbumin. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated to estimate 10-year risk of cardiovascular disease or stroke and the diabetes lifetime-perspective prediction (DIAL) score was calculated to estimate years free of cardiovascular disease.ResultsSix months after replacing exogenous insulin by DMR and GLP-1RA, visceral adipose tissue decreased significantly by 24%. Postprandial triglyceride and insulin concentrations decreased significantly (p < 0.001), as did total cholesterol (from median 3.64 (IQR 3.34–4.89) to 3.48 (3.18–3.97) mmol/l, p = 0.008), LDL (from median 1.92 (IQR 1.49–2.30) to 1.79 (1.49–2.08 mmol/l, p = 0.044), and urine microalbumin (from median 7 (IQR 3–27) to 4 (3–8) mg/l, p = 0.018). All daytime blood pressure values decreased significantly. The ASCVD 10-year risk score decreased (from median 13.6 (IQR 5.7–26.0) to 11.5 (4.2–22.5) %, p = 0.030)) and the DIAL score increased (from median 82 (IQR 81–83) to 83 (81–84) years, (p = 0.039)).DiscussionThe combination of DMR and GLP-1RA to replace insulin therapy in patients with T2DM is associated with a positive effect on multiple parameters of cardiovascular health. Taken together, they show a pattern of overall improvement in cardiovascular health, as evidenced by decreased risk scores for cardiovascular complications. However, it is not yet clear whether these improvements will translate into a true reduction in cardiovascular events.

Diets differing in carbohydrate cellularity and amount similarly reduced visceral fat in people with obesity - a randomized controlled trial (CARBFUNC)

Visceral adipose tissue (VAT) volume is associated with common lifestyle diseases. Dietary quality, including food matrix and degree of carbohydrate cellularity, as well as the carbohydrate/fat ratio, may influence VAT volume. We aimed to determine the effects of isocaloric diets differing in either "cellularity", a novel marker of dietary carbohydrate quality, or carbohydrate amount on visceral fat volume and anthropometric measures in adults with obesity. In a randomized controlled trial of 193 people with obesity/central adiposity, we compared changes in VAT volume after 6 and 12 months, measured by abdominal computed tomography, on three isocaloric eating patterns based on "acellular" carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), "cellular" carbohydrate sources (minimally processed foods with intact cellular structures such as fruits, potatoes/tubers, and rice), or low-carbohydrate high-fat (LCHF) principles. Outcomes were compared by an intention-to-treat (ITT) analysis using constrained linear mixed-effects modelling (cLMM) providing baseline-adjusted change scores and proper missing data handling without imputation. 78 and 57 participants completed 6 and 12 months, respectively, with similar intakes of energy (females: 1820-2060kcal, males: 2480-2550kcal) and protein (16-17 energy percent, E%) throughout the intervention, and only modest reductions in energy from baseline. Reported dietary intakes were 42-44, 41-42, and 11-15E% carbohydrate and 36-38, 37-38, and 66-70E% fat in the acellular, cellular and LCHF groups, respectively. There were no significant between-group differences in VAT volume after 6 months (cellular vs. acellular [95% CI]:-55cm³ [-545, 436]; LCHF vs. acellular [95% CI]:-225cm³ [-703, 253]) or after 12 months (cellular vs. acellular [95% CI]:-122cm³ [-757, 514]; LCHF vs. acellular [95% CI]:-317cm³ [-943, 309]). VAT volume decreased significantly within all groups by 14-18% and 12-17% after 6 and 12 months, respectively. Waist circumference was reduced to a significantly greater degree in the LCHF vs. acellular group at 6 months (LCHF vs. acellular [95% CI]:-2.78cm [-5.54,-0.017]). Despite modest energy restriction, the three isocaloric eating patterns, differing in carbohydrate cellularity and amount, decreased visceral fat volume significantly and to a similar clinically relevant degree. NCT03401970. https://clinicaltrials.gov/ct2/show/NCT03401970.

Determinants of hyperglucagonemia in pediatric non-alcoholic fatty liver disease.

ObjectiveOver the years, non-alcoholic fatty liver (NAFLD) disease has progressed to become the most frequent chronic liver disease in children and adolescents. The full pathology is not yet known, but disease progression leads to cirrhosis and hepatocellular carcinoma. Risk factors included hypercaloric diet, obesity, insulin resistance and genetics. Hyperglucagonemia appears to be a pathophysiological consequence of hepatic steatosis, thus, the hypothesis of the study is that hepatic fat accumulation leads to increased insulin resistance and impaired glucagon metabolism leading to hyperglucagonemia in pediatric NAFLD.Methods132 children and adolescents between 10 and 18 years, with varying degrees of obesity, were included in the study. Using Magnetic Resonance Imaging (MRI) average liver fat was determined, and patients were stratified as NAFLD (>5% liver fat content) and non-NAFLD (<5%). All patients underwent a standardized oral glucose tolerance test (OGTT). Additionally, anthropometric parameters (height, weight, BMI, waist circumference, hip circumference) such as lab data including lipid profile (triglycerides, HDL, LDL), liver function parameters (ALT, AST), uric acid, glucose metabolism (fasting insulin and glucagon, HbA1c, glucose 120 min) and indices evaluating insulin resistance (HIRI, SPISE, HOMA-IR, WBISI) were measured.ResultsChildren and adolescents with NAFLD had significantly higher fasting glucagon values compared to the non-NAFLD cohort (p=0.0079). In the NAFLD cohort univariate analysis of fasting glucagon was associated with BMI-SDS (p<0.01), visceral adipose tissue volume (VAT) (p<0.001), average liver fat content (p<0.001), fasting insulin concentration (p<0.001), triglycerides (p<0.001) and HDL (p=0.034). This correlation equally applied to all insulin indices HOMA-IR, WBISI, HIRI (all p<0.001) and SPISE (p<0.002). Multivariate analysis (R² adjusted 0.509) for the same subgroup identified HIRI (p=0.003) and VAT volume (p=0.017) as the best predictors for hyperglucagonemia. Average liver fat content is predictive in pediatric overweight and obesity but not NAFLD.ConclusionsChildren and adolescents with NAFLD have significantly higher fasting plasma glucagon values, which were best predicted by hepatic insulin resistance and visceral adipose tissue, but not average liver fat content.

Visceral, subcutaneous, and total fat mass accumulation in a prospective cohort of adolescents

Race and sex differences in adolescents' body fat are demonstrated in cross-sectional cohorts, yet a longitudinal design would better identify patterns of fat distribution over time. The aim was to examine race and sex differences in adiposity between black and white adolescents over 2 y. A cohort of adolescents aged 10-16 y (38% black; 52% girls; 15% overweight, 34% with obesity) underwent body composition measurements at baseline (n = 309) and 2 y later (n = 236), using DXA to quantify whole-body fat mass (FM) and MRI for abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) volumes. General linear models were used to examine race and sex differences in log-transformed FM, SAT, and VAT, adjusting for age, sexual maturation, extended BMI percentile, and race-by-sex interaction. SAT and VAT models in addition controlled for baseline FM and change in FM (for change models). Mean (95% CI) baseline FM (kg) was higher among white [18.5 (17.9, 19.2) than among black adolescents [17.4 (16.6, 18.2), P = 0.03] and girls [19.5 (18.8, 20.3) than boys [16.5 (15.8, 17.2), P < 0.0001]. Mean (95% CI) baseline SAT (L) was higher among girls [4.4 (4.2, 4.6)] than among boys [3.9 (3.7, 4.1), P < 0.0001]. Mean (95% CI) baseline VAT (L) was higher among white [0.5 (0.5, 0.6)] than among black [0.3 (0.3, 0.4)] adolescents (P < 0.0001) and boys [0.5 (0.4, 0.5)] than girls [0.4 (0.4, 0.4), P = 0.04]. Over 2 y mean (95% CI) FM change (kg) was higher among white [3.7 (2.9, 4.5)] than among black adolescents [2.3 (1.3, 3.3), P = 0.04] and girls [4.0 (3.0, 4.9)] than boys [2.0 (1.1, 3.0), P = 0.007], but SAT change (L) did not differ by race or sex. VAT change (L) was higher among white [0.1 (0.1, 0.1)] than among black adolescents [0.0 (0.0, 0.1), P = 0.003] and boys [0.1 (0.1, 0.1)] than girls [0.0 (0.0, 0.1), P = 0.034]. Sex and race differences in the deposition and accumulation of excess fat are important considerations for understanding obesity prevalence and obesity-related disease risk among adolescents.This trial was registered at clinicaltrials.gov as NCT02784509.

Quantification of chemotherapy-induced changes in body composition in pediatric, adolescent, and young adult lymphoma using standard of care CT imaging.

The objective of this study was to use computed tomography (CT) imaging to quantify chemotherapy-induced changes in body composition (BC) in pediatric, adolescent, and young adult (AYA) patients with lymphoma and to compare image-derived changes in BC measures to changes in traditional body mass index (BMI) measures. Skeletal muscle (SkM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) volumes were manually segmented using low-dose CT images acquired from a 10-year retrospective, single-site cohort of 110 patients with lymphoma. CT images and BMI percentiles (BMI%) were acquired from baseline and first therapeutic follow-up. CT image segmentation was performed at vertebral level L3 using 5 consecutive axial CT images. CT imaging detected significant treatment-induced changes in BC measures from baseline to first follow-up time points, with SAT and VAT significantly increasing and SkM significantly decreasing. BMI% measures did not change from baseline to first follow-up and were not significantly correlated with changes in image-derived BC measures. Patients who were male, younger than 12 years old, diagnosed with non-Hodgkin's lymphoma, and presented with stage 3 or 4 disease gained more adipose tissue and lost more SkM in response to the first cycle of treatment compared to their clinical counterparts. Standard of care CT imaging can quantify treatment-induced changes in BC that are not reflected by traditional BMI assessment. Image-based monitoring of BC parameters may offer personalized approaches to lymphoma treatment for pediatric and AYA patients by guiding cancer treatment recommendations and subsequently enhance clinical outcomes. • Standard of care low-dose CT imaging quantifies chemotherapy-induced changes in body composition in pediatric, adolescent, and young adults with lymphoma. • Body mass index could not detect changes in body composition during treatment that were quantified by CT imaging. • Pediatric and AYA patients who were male, younger than 12 years old, and diagnosed with non-Hodgkin's lymphoma, and presented with stage 3 or 4 disease gained more adipose tissue and lost more skeletal muscle tissue in response to the first cycle of treatment compared to their clinical counterparts.

Utilizing Computed Tomography to Analyze the Morphomic Change between Patients with Localized and Metastatic Renal Cell Carcinoma: Body Composition Varies According to Cancer Stage.

Background: This study aimed to elucidate the change of body composition in different clinical stages of renal cell carcinoma (RCC) by analyzing computed tomography (CT) images. Methods: We enrolled patients diagnosed with RCC in a tertiary medical center who did not mention body weight loss or symptoms of cachexia. We grouped patients into those with localized RCC and those with metastatic RCC. Analyses of the volume of skeletal muscles tissue (SMT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) calculated based on CT images were performed and included subgroup analyses by sex and age. The correlation between tumor size and body composition in localized RCC was also examined. Results: A total of 188 patients were enrolled in this study. There was significantly lower VAT (p = 0.015) in the metastatic group than in the localized group. SAT, body weight, and body mass index (BMI) were not significantly different between these two groups. In the subgroup analysis, a significant difference in SMT and VAT was noted in the male and younger subgroups but not in the female and older subgroups. Regarding primary tumor size in localized RCC, VAT was significantly higher in patients with larger tumors (p = 0.003). Conclusions: In localized RCC, VAT volume was significantly larger in those with large primary tumor size. However, the VAT was significantly lower in those with metastatic status comparing to those with localized disease. The clinical course of cancers closely correlates with body composition.

Ectopic fat is associated with cardiac remodeling-A comprehensive assessment of regional fat depots in type 2 diabetes using multi-parametric MRI.

BackgroundDifferent regional depots of fat have distinct metabolic properties and may relate differently to adverse cardiac remodeling. We sought to quantify regional depots of body fat and to investigate their relationship to cardiac structure and function in Type 2 Diabetes (T2D) and controls.MethodsFrom the SCAPIS cohort in Linköping, Sweden, we recruited 92 subjects (35% female, mean age 59.5 ± 4.6 years): 46 with T2D and 46 matched controls. In addition to the core SCAPIS data collection, participants underwent a comprehensive magnetic resonance imaging examination at 1.5 T for assessment of left ventricular (LV) structure and function (end-diastolic volume, mass, concentricity, ejection fraction), as well as regional body composition (liver proton density fat fraction, visceral adipose tissue, abdominal subcutaneous adipose tissue, thigh muscle fat infiltration, fat tissue-free thigh muscle volume and epicardial adipose tissue).ResultsCompared to the control group, the T2D group had increased: visceral adipose tissue volume index (P < 0.001), liver fat percentage (P < 0.001), thigh muscle fat infiltration percentage (P = 0.02), LV concentricity (P < 0.001) and LV E/e'-ratio (P < 0.001). In a multiple linear regression analysis, a negative association between liver fat percentage and LV mass (St Beta −0.23, P < 0.05) as well as LV end-diastolic volume (St Beta −0.27, P < 0.05) was found. Epicardial adipose tissue volume and abdominal subcutaneous adipose tissue volume index were the only parameters of fat associated with LV diastolic dysfunction (E/e'-ratio) (St Beta 0.24, P < 0.05; St Beta 0.34, P < 0.01, respectively). In a multivariate logistic regression analysis, only visceral adipose tissue volume index was significantly associated with T2D, with an odds ratio for T2D of 3.01 (95% CI 1.28–7.05, P < 0.05) per L/m2 increase in visceral adipose tissue volume.ConclusionsEctopic fat is predominantly associated with cardiac remodeling, independently of type 2 diabetes. Intriguingly, liver fat appears to be related to LV structure independently of VAT, while epicardial fat is linked to impaired LV diastolic function. Visceral fat is associated with T2D independently of liver fat and abdominal subcutaneous adipose tissue.

Silhouette images enable estimation of body fat distribution and associated cardiometabolic risk

Inter-individual variation in fat distribution is increasingly recognized as clinically important but is not routinely assessed in clinical practice, in part because medical imaging has not been practical to deploy at scale for this task. Here, we report a deep learning model trained on an individual’s body shape outline—or “silhouette” —that enables accurate estimation of specific fat depots of interest, including visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes, and VAT/ASAT ratio. Two-dimensional coronal and sagittal silhouettes are constructed from whole-body magnetic resonance images in 40,032 participants of the UK Biobank and used as inputs for a convolutional neural network to predict each of these quantities. Mean age of the study participants is 65 years and 51% are female. A cross-validated deep learning model trained on silhouettes enables accurate estimation of VAT, ASAT, and GFAT volumes (R2: 0.88, 0.93, and 0.93, respectively), outperforming a comparator model combining anthropometric and bioimpedance measures (ΔR2 = 0.05–0.13). Next, we study VAT/ASAT ratio, a nearly body-mass index (BMI)—and waist circumference-independent marker of metabolically unhealthy fat distribution. While the comparator model poorly predicts VAT/ASAT ratio (R2: 0.17–0.26), a silhouette-based model enables significant improvement (R2: 0.50–0.55). Increased silhouette-predicted VAT/ASAT ratio is associated with increased risk of prevalent and incident type 2 diabetes and coronary artery disease independent of BMI and waist circumference. These results demonstrate that body silhouette images can estimate important measures of fat distribution, laying the scientific foundation for scalable population-based assessment.

Effect of Incorporating 1 Avocado Per Day Versus Habitual Diet on Visceral Adiposity: A Randomized Trial.

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short-term well-controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel-arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free-living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [-0.024 L, 0.058 L], P=0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high-sensitivity C-reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low-density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low-density lipoprotein concentrations, and total cholesterol:high-density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free-living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

MRI characterization of skeletal muscle size and fatty infiltration in long-term trained and untrained individuals.

This study investigated body composition measures in highly trained and untrained individuals using whole‐body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty‐six individuals were included: endurance‐trained males (ME, n = 8) and females (FE, n = 7), strength‐trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross‐sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males.

Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results – using MRI-derived, BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

The Optimal Axial Anatomical Site for a Single-Slice Area to Quantify the Total Volume of Visceral Adipose Tissue in Quantitative CT.

PurposeDetermine the association between cross-sectional visceral adipose tissue (VAT) area of different anatomic locations and total abdominopelvic VAT volume; identify the optimal measurement site in a single-slice to quantify the total VAT volume.MethodParticipants who underwent non-contrast abdominal scan by quantitative CT (QCT) were enrolled from May 2021 to October 2021. The VAT area (cm2) at different anatomic sites as upper-pole, lower-pole, and hilum of the kidney, intervertebral disc of L2/L3 and L5/S1, and umbilical level were measured on QCT PRO BMD workstation (Mindways QCT PRO workstation). The total VAT volume (cm3) from the upper pole of kidney to the L5/S1 intervertebral disc of the pelvis (abdominopelvic region) was obtained by using Siemens Healthineers Syngo via Frontier cardiac risk assessment. Regression models were used to identify the optimal single-slice in different gender for estimating VAT volume. Statistical significance was established at P < 0.05.ResultsTotal of 311 Chinese participants including 179 men [age, 55.1 ± 14.9 years; body mass index (BMI), 24.2 ± 3.2 kg/m2; total VAT volume, 2482.6 ± 1276.5 mL] and 132 women [age, 54.3 ± 14.9; BMI, 23.5 ± 2.9; total VAT volume, 1761.5 ± 876.4]. Pearson’s correlation analysis revealed a strong association between the VAT area and total abdominopelvic VAT volume at the hilum of the kidney in both men (r=0.938, P<0.001) and women (r=0.916, P<0.001). Adjust for covariates including age, BMI, and waist circumference make a relatively small effect on predicting the total VAT volume.ConclusionsMeasurement of cross-sectional areas at the hilum of the kidney in both genders showed a strongest relation to TVAT volume. Our results may provide an identifiable and valuable axial landmark for measuring visceral adipose tissue in clinical practice.

Abstract 5818: Features of cancer cachexia in non-small cell lung cancer: Insights from the prospective TRACERx study

Abstract Introduction: Cancer cachexia (CC) is a major contributor to morbidity and mortality in patients with non-small cell lung cancer (NSCLC). It is characterized by loss of skeletal muscle (SM) tissue with or without adipose tissue loss. This analysis reports on the characteristics and outcomes of patients recruited into the prospective TRACERx study, who presented with or subsequently developed features of CC during follow-up. Approach: Using longitudinal CT imaging, total, subcutaneous and visceral adipose tissue (TAT, SAT, VAT) and SM volumes were manually quantified at the 3rd lumbar vertebrae level. Body weight was measured every 3-6 months and grouped according to BMI-adjusted weight loss grades. Multi-region primary tumour tissue was collected at the time of surgical resection and subjected to whole exome and RNA sequencing. Results: Patients in the TRACERx 421 cohort who presented with low SAT volume at diagnosis, represented by the lower 20% percentile of the cohort, had significantly shorter lung-cancer specific survival (LCSS) and overall survival (OS) compared with patients in the 80% percentile (3-y LCSS 61% vs 81%, p&amp;lt;0.001; 3-y OS 57% vs 69%, p=0.02). Patients presenting with low VAT had a significantly shorter LCSS (3-y-LCSS 66% vs 79%, p=0.01), but not OS (3-y OS 60% vs 69%). Low SM volume was not associated with LCSS or OS. However, loss of SM volume of ≥20% between diagnosis and disease relapse was associated with significantly reduced LCSS and OS (3-y LCSS 30% vs 49%, p=0.02; 3-y OS 26% vs 45%, p=0.03). Based on a multivariable model, low SAT volume at diagnosis and SM loss were independent prognostic factors for LCSS, but not OS. In addition, BMI-adjusted weight loss was associated with shorter OS and LCSS (3-y OS 7% for patients with weight loss grade 4 vs 54% in patients with stable weight, p&amp;lt;0.001 [LCSS 8% vs 61%, p&amp;lt;0.001]). Preliminary genomic data from patients with disease recurrence and with (n=47) or without (n=107) features of CC, defined as SAT or muscle loss &amp;gt;20% or weight loss grade 4, demonstrated distinct copy number alteration and differential gene expression profiles. Conclusion: In patients with early-stage NSCLC, both altered body composition and weight loss in keeping with CC was associated with poor survival outcomes. In particular, low SAT volume at diagnosis and loss of SM between diagnosis and relapse were independent prognostic factors for LCSS. Ongoing analyses in TRACERx will continue to investigate the potential tumour-intrinsic mediators of CC. Citation Format: Othman Al-Sawaf, Marcin Skrzypski, Jakob Weiss, Takahiro Karasaki, Nicolai Juul Birkbak, Francisco Zambrana, Alexander Frankell, Thomas B. Watkins, Carlos Martinez Ruiz, Selvaraju Veeriah, Cristina Naceur-Lombardelli, TRACERx Consortium, Nicholas McGranahan, Hugo Aerts, Charles Swanton, Mariam Jamal-Hanjani. Features of cancer cachexia in non-small cell lung cancer: Insights from the prospective TRACERx study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5818.

Improvement of Pancreatic Steatosis and Indices of Insulin Resistance After Metabolic Surgery.

PurposeObesity is associated with fat accumulation in ectopic sites such as the pancreas, the so-called pancreatic steatosis (PS). Bariatric surgery has been shown to be associated with reducing pancreatic fat. This study investigated the effect of laparoscopic sleeve gastrectomy (LSG) on pancreatic volume and its fat content and glucose homeostasis.MethodsThe study enrolled 54 patients subjected to LSG. Metabolic variables and pancreatic exocrine function were assessed immediately before surgery and 12 months after. MRI of the abdomen was performed to measure pancreatic fat content and its total volume and visceral adipose tissue (VAT).ResultsSurgery resulted in a significant reduction in body weight and BMI. HbA1c, fasting insulin, C-peptide levels, HOMA-IR, and Hs-CRP levels decreased significantly. Surgery resulted in significant improvement in lipid profile except for HDL-cholesterol and liver function tests. Total VAT volume decreased significantly. Total pancreas volume decreased by a mean of 9.0 cm3 (95% CI: 6.6–11.3). The median change of pancreatic fat was −26.1% (range: −55.6 to 58.3%). Pancreatic lipase decreased significantly (P < 0.001). There was a positive correlation between the percentage of total weight loss and decrease in pancreatic fat volume (r = 0.295, P = 0.030).ConclusionWeight loss after LSG is associated with a reduction of total VAT volume, total pancreatic volume, and pancreatic fat content. These changes are associated with improved glucose homeostasis, reduced systemic inflammation, and decreased pancreatic lipase secretion.

Relationship of Subcutaneous Adipose Tissue Inflammation-Related Gene Expression With Ectopic Lipid Deposition in Persons With HIV.

Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART. A total of 92 PWH with well-controlled viremia underwent computed tomography imaging and abdominal SAT biopsy for gene expression analysis. SAT gene expression was measured using a NanoString panel of 255 immune-related genes. Associations between gene expression and computed tomography measurements of the volume and attenuation (radiodensity) of metabolically relevant ectopic fat depots were assessed using multivariable linear regression and network analysis. Greater SAT volume was associated with higher visceral and pericardial adipose tissue volume, but lower skeletal muscle attenuation. Lower SAT attenuation, a measure of lipid content, was associated with lower visceral adipose tissue attenuation. Hierarchical clustering identified a subset of macrophage-related genes in SAT, including CCL2, CCL22, CCL13, CCR1, CD86, CD163, IL-6, IL-10, MRC1, and TREM2, which were associated with an increased lipid deposition in multiple ectopic depots. Altered expression of macrophage-related genes in SAT is associated with differences in ectopic fat depot morphometrics among PWH on long-term ART, including in the pericardial and visceral compartments. These findings provide basis for future studies to assess host, virus, and treatment factors shaping the SAT immune environment and its effects on morphometric changes and metabolic comorbidities in PWH.

Comparison of the risk of cardiovascular diseases, stroke, and diabetes among the selected group of football referees and the group of general population men from Northern Poland - a pilot study.

We aimed at comparing the total body fat and visceral adipose tissue content in football referees and in the control group of general population men. An assessment of compliance with health promoting behavior in both groups was carried out. This study, conducted in Northern Poland, involved 112 men. The study group comprised 56 men, football referees. The control group consisted of randomly chosen general population men, not engaged in any sport activities. Assessment of compliance with health promoting behavior among football referees and general population men was based on ultrasound imaging using the BodyMetrix System device (IntelaMetrix, Poland). The study employed a survey questionnaire comprised of the original section and two standardized questionnaires: the Health Behavior Inventory (HBI) and the NEO-Five Factor Inventory (NEO-FFI): the Health Behavior Inventory (HBI) and the NEO-Five Factor Inventory (NEO-FFI). The visceral adipose tissue content in the study group (football referees) was found to be low, and the excess of body fat was 0-0.25 kg. In the control group, the trunk fat volume was found to be higher by more than 8% as compared with the study group. Also, the level of visceral adipose tissue was high, and the excess of body fat was 0-4 kg. Thanks to properly planned and systematically continued physical activity, despite non-compliance with certain pro-health principles (increased sweet supply and consumption of alcoholic beverages), football referees are characterized by the correct body fat volume and low level of visceral adipose tissue. The parameters were found to be markedly higher in the control group of randomly selected men from the general population. The risk of diabetes, stroke, and cardiovascular diseases among football referees was found to be very low.

Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial

Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist under development for the treatment of type 2 diabetes. The aim of this substudy was to characterise the changes in liver fat content (LFC), volume of visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT) in response to tirzepatide or insulin degludec in a subpopulation of the SURPASS-3 study. This substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial was done at 45 medical research centres and hospitals across eight countries (Argentina, Austria, Greece, Hungary, Italy, Romania, Spain, and the USA). Eligible participants were adults with type 2 diabetes, a baseline HbA1c 7·0-10·5% (53-91 mmol/mol), a BMI of at least 25 kg/m2, stable weight, were insulin-naive, and on treatment with metformin alone or in combination with a SGLT2 inhibitor for at least 3 months before screening. In addition to the main study inclusion criteria, substudy participants had a fatty liver index of at least 60. Participants had an MRI scan and were randomised (1:1:1:1) in the main study to subcutaneous injection once per week of tirzepatide 5 mg, 10 mg, or 15 mg, or subcutaneous injection once per day of titrated insulin degludec, using an interactive web-response system, and were stratified by country, HbA1c, and concomitant oral anti-hyperglycaemic medication. The primary efficacy endpoint was the change from baseline in LFC (as measured by MRI-proton density fat fraction [MRI-PDFF]) at week 52 using pooled data from the tirzepatide 10 mg and 15 mg groups versus insulin degludec. Analyses were assessed in the enrolled MRI population, which consisted of participants in the modified intention-to-treat population of the main study who also had a valid MRI at either baseline or after baseline. This is a substudy of the trial registered with ClinicalTrials.gov, number NCT03882970, and is complete. From April 1, 2019, to Nov 15, 2019, 502 participants were assessed for eligibility to participate in this substudy, 296 (59%) of whom were included in the enrolled MRI population and randomly assigned to treatment (tirzepatide 5 mg, n=71; tirzepatide 10 mg, n=79; tirzepatide 15 mg, n=72; and insulin degludec, n=74). Baseline demographics and clinical characteristics were similar across all treatment groups. From an overall mean baseline LFC of 15·71% (SD 8·93), the absolute reduction in LFC at week 52 was significantly greater for the pooled tirzepatide 10 mg and 15 mg groups (-8·09%, SE 0·57) versus the insulin degludec group (-3·38%, 0·83). The estimated treatment difference versus insulin degludec was -4·71% (95% CI -6·72 to -2·70; p<0·0001). The reduction in LFC was significantly correlated (p≤0·0006) with baseline LFC (ρ=-0·71), reductions in VAT (ρ=0·29), reductions in ASAT (ρ=0·33), and reductions in body weight (ρ=0·34) in the tirzepatide groups. Tirzepatide showed a significant reduction in LFC and VAT and ASAT volumes compared with insulin degludec in this subpopulation of patients with type 2 diabetes in the SURPASS-3 study. These data provide additional evidence on the metabolic effects of this novel dual GIP and GLP-1 receptor agonist. Eli Lilly and Company.

Exercise may impact on lumbar vertebrae marrow adipose tissue: Randomised controlled trial.

Animal and human cross-sectional data suggest that bone marrow adipose tissue (MAT) may respond to mechanical loads and exercise. We conducted the first randomised controlled trial of exercise on MAT modulations in humans. Forty patients with chronic non-specific low back pain (NSCLBP) were enrolled in a six-month single-blinded randomised controlled trial (ACTRN12615001270505). Twenty patients loaded their spines via progressive upright aerobic and resistance exercises targeting major muscle groups (Exercise). Twenty patients performed non-weightbearing motor control training and manual therapy (Control). Testing occurred at baseline, 3-months (3mo) and 6-months (6mo). Lumbar vertebral fat fraction (VFF) was measured using magnetic resonance imaging axial mDixon sequences. When compared to baseline (percent change), lumbar vertebral fat fraction (VFF; measured using magnetic resonance imaging axial mDixon sequences) was lower in Exercise at 3mo at L2 (-3.7[6.8]%, p=0.033) and L4 (-2.6[4.1]%, p=0.015), but not in Control. There were no between-group effects. The effects of Exercise on VFF were sex-specific, with VFF lower in men at L2, L3, L4 at 3mo and at L1, L2, L3 and L4 at 6mo (p all≤0.05), but not in women. Leg and trunk lean mass were increased at 3mo in Exercise. Changes in VFF correlated significantly with changes in total fat (ρ=0.40) and lean (ρ=-0.41) masses, but not with lumbar BMD (ρ=-0.10) or visceral adipose tissue volume (ρ=0.23). This trial provided first prospective evidence in humans that a moderate exercise intervention may modulate lumbar VFF as a surrogate measure of MAT at 3mo, yet not 6mo. The effect of exercise on MAT may be more prominent in males than females.