Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies

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

Increased Glucose Uptake in Visceral Versus Subcutaneous Adipose Tissue Revealed by PET Imaging

The Effect and Mechanism of Subcutaneous and Visceral Adipose Tissue Loss on Gastric Cancer Patients With Cachexia

The association of adipose tissue area with subclinical coronary atherosclerosis progression in men with and without HIV.

Targeted lipidomics and transcriptomics profiling reveal the heterogeneity of visceral and subcutaneous white adipose tissue

Obesity is a major driver of cardiometabolic risk. Abdominal visceral adipose tissue (VAT) and sc adipose tissue (SAT) may confer differential metabolic risk profiles. We investigated the relations of VAT and SAT with cardiometabolic risk factors in the Jackson Heart Study cohort. Participants from the Jackson Heart Study (n=2477; 64% women; mean age, 58 yr) underwent multidetector computed tomography, and the volumetric amounts of VAT and SAT were assessed between 2007 and 2009. Cardiometabolic risk factors were examined by sex in relation to VAT and SAT. Men had a higher mean volume of VAT (873 vs. 793 cm3) and a lower mean volume of SAT (1730 vs. 2659 cm3) than women (P=0.0001). Per 1-sd increment in either VAT or SAT, we observed elevated levels of fasting plasma glucose and triglyceride, lower levels of high-density lipoprotein-cholesterol, and increased odds ratios for hypertension, diabetes, and metabolic syndrome. The effect size of VAT in women was larger than that of SAT [fasting plasma glucose, 5.51±1.0 vs. 3.36±0.9; triglyceride, 0.17±0.01 vs. 0.05±0.01; high-density lipoprotein-cholesterol, -5.36±0.4 vs. -2.85±0.4; and odds ratio for hypertension, 1.62 (1.4-1.9) vs. 1.40 (1.2-1.6); diabetes, 1.82 (1.6-2.1) vs. 1.58 (1.4-1.8); and metabolic syndrome, 3.34 (2.8-4.0) vs. 2.06 (1.8-2.4), respectively; P<0.0001 for difference between VAT and SAT]. Similar patterns were also observed in men. Furthermore, VAT remained associated with most risk factors even after accounting for body mass index (P ranging from 0.006-0.0001). The relationship of VAT to most risk factors was significantly different between women and men. Abdominal VAT and SAT are both associated with adverse cardiometabolic risk factors, but VAT remains more strongly associated with these risk factors. The results from this study suggest that relations with cardiometabolic risk factors are consistent with a pathogenic role of abdominal adiposity in participants of African ancestry.

Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.

Introduction: Excess visceral adipose tissue (VAT) robustly predicts incident cardiometabolic risk, independent of body mass index (BMI), and this association is stronger in women than in men. Cross-sectional studies suggest that VAT accrual accelerates in older women as compared to similarly aged men, in concert with menopausal changes, which may help to explain the greater effect of VAT on subsequent disease risk observed in women. However, a direct test of sex differences in the rate of VAT accrual requires longitudinal VAT data which have been largely lacking. Objectives: This analysis evaluated sex differences in the rate of VAT accrual in adults. Secondary analyses examined differences in the rate of VAT accrual in pre-, peri-, and post-menopausal women. Methods: Participants were 532 (59% female) non-Hispanic white adults, aged 18-84 years at baseline, who were enrolled in a study of normative changes in body composition over the lifespan. Abdominal VAT mass and subcutaneous adipose tissue (SAT) mass were assessed using multiple-image magnetic resonance imaging at two time points, with an average follow-up of 7.2 ± 2.5 years. Linear regression models were used to examine the effects of sex, baseline age, and their interaction on rate of change per year in body composition measures (ΔBMI, ΔVAT, and ΔVAT/SAT ratio (ΔVSR)) independent of baseline body composition measures and baseline visit year. Secondary analyses examined differences in these rates of change by baseline menopausal status (pre, peri, post), after adjustment for baseline age. Results: Levels of BMI, VAT, and VSR all increased over the follow-up period on average; however, the change in BMI (mean ΔBMI = +0.5%) was far smaller than for VAT (mean ΔVAT=+6.3%) and VSR (mean ΔVSR = +3.4%). ΔVAT and ΔBMI decreased linearly with age in both sexes (p&lt;0.001), such that older individuals had lower rates of VAT and BMI gain, and this deceleration in VAT and BMI accrual was greater in men than women (p for interaction 0.007 and 0.038, respectively). ΔVSR did not vary with age in either sex, but remained higher in men than women throughout adulthood. ΔBMI, ΔVAT, and ΔVSR did not differ by baseline menopausal status. Conclusions: VAT mass increased with age in both men and women, but the rate of VAT gain gradually declined with advancing age. There was no evidence of accelerated VAT accrual during menopause as previously reported in the literature. However, the rate of VAT gain was more consistent in women during adulthood than in men, who exhibited greater deceleration. Future work will explore whether this sex difference in the pattern of body composition change explains the differential effects of VAT on disease risk in men and women.

Obesity is associated with insulin resistance and other metabolic changes that might be modified by overfeeding diets with different protein levels. The objective of the study was to determine the effect of overfeeding diets with 5%, 15%, or 25% energy from protein on insulin sensitivity and compartments of body fat in healthy men and women. Fifteen men and five women were overfed by approximately 40% for 56 days with 5% (low protein), 15% (normal protein), or 25% (high protein) protein diets. Insulin sensitivity was measured using a two-step insulin clamp at baseline and at 8 weeks. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and multislice computed tomography scan and abdominal sc fat cell size was determined on osmium-fixed fat cells. This was an in-patient metabolic ward study. Insulin sensitivity and free fatty acids during low and high levels of insulin infusion before and after 8 weeks after overfeeding and changes in body fat distribution from computed tomography were measured. Total body fat mass, fat-free mass (FFM), visceral adipose tissue (VAT), and deep sc fat all increased with overfeeding. FFM and intrahepatic lipid increased more on the high protein diet, whereas percentage BF and fasting free fatty acids (FFAs) increased more on the low protein diet. Baseline fat cell size predicted the increase in VAT and the magnitude of FFA suppression during the high-dose insulin clamp. Acute release of insulin at baseline predicted the increase in deep sc fat but not VAT. Fasting insulin and glucose increased with overfeeding, but glucose disposal as measured by the clamp was not changed. Suppression of FFAs was less complete during the high-dose insulin infusion after overfeeding. Eight weeks of overfeeding, which increased fat mass including expansion of visceral and deep sc tissues and intrahepatic lipid, increased fasting insulin and glucose, impaired the suppression of FFA but did not produce whole-body insulin resistance.

Monocyte/macrophage-specific soluble CD163 (sCD163) concentration is associated with insulin resistance and increases with deteriorating glycemic control independently of BMI. This led to the proposal of the hypothesis that obesity-associated white adipose tissue inflammation varies between individuals. The objective was to examine the effect of male overweight/obesity and type 2 diabetes mellitus (T2DM) on associations between adiposity parameters and sCD163. A total of 23 overweight/obese non-diabetic men, 16 overweight/obese men with T2DM, and a control group of 20 normal-weight healthy men were included. Body composition and regional body fat distribution were determined by whole-body dual X-ray absorptiometry scan and abdominal computed tomography (CT) scan. Serum sCD163 concentrations were determined by ELISA. Associations between adiposity parameters and sCD163 were investigated using multiple linear regression analysis. In the normal-weight healthy men, there was no significant association between adiposity parameters and sCD163, whereas in the overweight/obese non-diabetic men, measures of general and regional adiposity were positively associated with sCD163. In the overweight/obese men with T2DM, only visceral adipose tissue (VAT) and the ratio of VAT to abdominal subcutaneous adipose tissue (SAT), a measure of relative body fat distribution between VAT and SAT depots, were positively associated with sCD163. In a multivariate analysis, including VAT, upper-body SAT, and lower-body fat, adjusted for BMI and age, VAT remained a significant predictor of sCD163 in the overweight/obese T2DM men, but not in the overweight/obese non-diabetic men. Our results indicate that VAT inflammation is exaggerated in men with T2DM, and that propensity to store excess body fat viscerally is particularly detrimental in men with T2DM.

BackgroundBrain age – an image derived measure from structural brain images on T1 weighted scans may reveal information on Alzheimer’s risk. We have previously shown that increased abdominal adipose tissue relates to brain atrophy. We evaluated the links between abdominal adipose tissue and brain age.MethodA total of 1,164 healthy participants from four sites (mean chronological age 55.17 ± 12.37 years, 52% women; 48% men; 39% non‐white) were scanned on 1.5T MR machines with a whole‐body protocol. Whole body sequences utilized in the quantitative analyses of abdominal fat were coronal T1 were used to segment visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) segmentation. In this process, a nnU‐Net model was used for fully supervised segmentation and ITK‐SNAP was used for manual annotation. Brain age was computed using a regression‐based 3D Simple Fully Convolutional Network. The model was trained on in‐house T1‐weighted MRI scans collected from 5,500 healthy individuals, aged 18 to 89 years. Brain age gap (BAG) was computed by subtracting chronological age from brain age. Bivariate correlations between VAT and SAT to chronological and brain age were done with partial correlations adjusted for sex with brain age. VAT and SAT were normalized to total abdominal body fat volume. Chronological age was not adjusted for in brain age models to avoid collinearity.ResultMean brain age exceeded chronological age (mean brain age = 56.04 ± 12.65, mean BAG = 0.69) and were highly correlated (r=0.94, p <.001). VAT and SAT were positively related to increased chronological age (VAT: r=0.2780, p = 5.477e‐20; r=0.0924, p = 0.002817) and increased brain age (VAT: r=0.2806, p = 2.42e‐20; SAT: r=0.0947, p = 0.002189) with VAT being more closely linked to age than SAT. This did not change when adjusting for sex in separate partial correlations between VAT and SAT for brain age (VAT: rp = r=0.2948, p = 2.247e‐22; SAT: r=0.1070, p = 0.0005353). No statistically significant link was noted with VAT, SAT, and BAG.ConclusionBoth VAT and SAT are linked to chronological and brain age with VAT being more strongly linked. VAT may be a key target for modifying brain age and Alzheimer’s risk.

Visceral fat accumulation is an indicator of adipose tissue macrophage infiltration in women

The accumulation of adipose tissue in 2 regional fat depots, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), have a differential impact on bone mineral density (BMD). In most studies, a positive association of SAT with bone density has been reported. There are conflicting data on the effect of VAT on bone. One recent study suggested that VAT was a negative and SAT a positive predictor of bone structural parameters in young adults. Various chemicals secreted from VAT and SAT appear to mediate these associations with bone but there is a limited knowledge of their role. Potential mediators include inflammatory cytokines such as IL-6, soluble intercellular adhesion molecules such as E-selectin, and adipokine hormones such as adiponectin and leptin. IL-6 and adiponectin can increase osteoclast activity and appear to have deleterious effects on BMD. In a previous report, VAT was an independent predictor of E-selectin and soluble intercellular adhesion molecule 1 (sICAM1), whereas SAT was a predictor of IL-6, and both SAT and VAT predicted adiponectin levels. Other studies have shown that VAT is an important determinant of levels of sICAM1 and E-selectin in obese and normal-weight girls. This cross-sectional study investigated associations of VAT and SAT and potential chemical mediators with BMD in adolescent obese and normal-weight girls. The investigators tested the hypothesis that adolescent girls with a greater VAT to SAT ratio would have lower bone density measures mediated by inflammatory cytokines, adiponectin, and leptin. Fifteen obese girls 12 to 18 years old were matched to 15 normal-weight controls for race, ethnicity, and bone age (within 2 year). Magnetic resonance imaging was used to measure SAT and VAT at the lumbar level. Dual-energy x-ray absorptiometry assessed bone density at the spine, hip, and whole body. Fasting serum levels of leptin, adiponectin, E-selectin, sICAM, and IL-6 were determined. The mean body mass index SD score was higher in obese subjects than in controls (3.7 ± 1.5 versus 0.1 ± 0.4 kg/m2). After controlling for SAT, VAT was a negative predictor of whole-body BMD and bone mineral content/height in the whole group, and of BMD, bone mineral apparent density, whole-body BMD, and bone mineral content/height in obese girls. As hypothesized, obese girls with the highest VAT to SAT ratio had the lowest bone density measures. E-selectin and adiponectin were negative predictors for BMD, and leptin was a positive predictor in a regression model including VAT/SAT, adipokines, and cytokines. These findings indicate that VAT is a negative predictor of bone density in obese girls. Pro-inflammatory adhesion molecules such as E-selectin and adipokines such as adiponectin and leptin appear to mediate the association between VAT and bone density.

Recent studies have shown that a high breast volume predicts visceral adipose tissue (VAT) and risk for type 2 diabetes independently of body mass index (BMI) and waist circumference (WC). To investigate the relationships between breast adipose tissue (BrAT), body fat distribution and cardiometabolic risk factors. In all, 97 healthy females (age 19-46 years, BMI 16.8-46.8 kg/m2) were examined cross-sectionally. A subgroup of 57 overweight and obese women (BMI 34.7±4.5 kg/m2) was investigated before and after diet-induced weight loss (-8.3±4 kg). Fat mass (FM) was measured by air-displacement plethysmography. Volumes of BrAT, VAT and subcutaneous adipose tissue (SAT) of the trunk and extremeties were assessed by whole-body magnetic resonance imaging (MRI). Cardiometabolic risk was assessed by lipid profile, fasting glucose, insulin, adiponectin and leptin levels. A high proportion of BrAT was associated with higher truncal and lower leg SAT. Weight loss-induced decline in BrAT as a percentage of total adipose tissue was correlated with decreases in SAT(trunk) and inversely with SAT(legs) and VAT. No relationships were found between BrAT and cardiometabolic risk factors. By contrast, SAT(trunk) and VAT showed positive and SAT(legs) inverse associations with cardiometabolic risk factors in cross-sectional as well as longitudinal analysis. The association between BrAT and VAT was lost after adjusting for %FM and truncal SAT. Our results indicate that high BrAT reflects a phenotype with increased SAT(trunk) and low SAT(legs). BrAT showed no independent relationships with VAT and cardiometabolic risk factors.

Background and objectivesBody composition (BC) assessment by computed tomography (CT) at the level of the third lumbar vertebra (L3) is considered the gold standard for evaluating muscle and adipose compartments. However, manual segmentation is time-consuming and impractical for large data sets. This study aimed to compare the automated method, Identificação Automatizada da Composição Corporal (IACC), with manual segmentation performed using 3D Slicer.MethodsThis retrospective cross-sectional study included 126 participants, each contributing one single axial CT slice at the L3 level, obtained from routine clinical CT scans acquired between November 2023 and January 2025. Manual segmentations were performed in 3D Slicer by a trained evaluator and validated by an experienced radiologist. The IACC automatically identified the L3 level and segmented skeletal muscle (MUSCLE), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). Analyses included intra- and inter-rater reproducibility (ICC, Dice coefficient), Pearson correlation, agreement (ICC), and Bland–Altman plots. ResultsThe mean analysis time was approximately 5 min per scan with IACC, compared with 25–30 min using the manual method. Intra-rater reproducibility was excellent (ICC > 0.99), and inter-rater agreement demonstrated high Dice coefficients for SAT (0.982), skeletal muscle (0.940), and VAT (0.932). Concordance between methods was high for SAT (ICC = 0.932) and VAT (ICC = 0.958), and good for skeletal muscle (ICC = 0.784), all with Pearson’s r > 0.97. Bland–Altman analysis showed minimal mean bias for VAT (− 0.35 cm2) and small variability for SAT, indicating excellent agreement for adipose tissue compartments. In contrast, skeletal muscle presented greater disagreement, with a larger negative bias and wider limits of agreement, reflecting higher variability in automated measurements.ConclusionsIACC demonstrated high accuracy and efficiency for automated segmentation of SAT and muscle, substantially reducing analysis time compared to manual segmentation. Although greater variability was observed for skeletal muscle measurements, the tool shows promise for use in large-scale population studies and potential clinical applications, particularly, where rapid and standardized analyses are required.