Glucose metabolism and radiodensity of abdominal adipose tissue: A 5-year longitudinal study in a large PET cohort.

OBJECTIVE: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) allows noninvasive assessment of glucose metabolism and radiodensity in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We aimed to address the effects of ageing and metabolic factors on abdominal adipose tissue. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analyzed data from 435 healthy men (mean 42.8 years) who underwent a health check-up programme twice, at baseline and the 5-year follow-up. The mean standardized uptake value (SUV) was measured using SAT and VAT and divided by the liver SUV. The mean Hounsfield units (HU) of the SAT and VAT were measured from the CT scans. The effects of clinical variable clusters on SUVR were investigated using Bayesian hierarchical modelling; metabolic cluster (BMI, waist-to-hip ratio, fat percentage, muscle percentage*-1, HOMA-IR), blood pressure (systolic, diastolic), glucose (fasting plasma glucose level, HbA1c) and C-reactive protein. RESULTS: All the clinical variables changed during the 5-year follow-up period. The SUVR and HU of the VAT increased during follow-up; however, those of the SAT did not change. SUVR and HU were positively correlated with both VAT and SAT. SAT and VAT SUVR were negatively associated with metabolic clusters. CONCLUSIONS: Ageing led to increased glucose metabolism and radiodensity in VAT, but not in SAT. VAT may reflect the ageing process more directly than SAT. Glucose metabolism was higher and radiodensity was lower in VAT than in SAT, probably owing to differences in gene expression and lipid density. Both glucose metabolism and radiodensity of VAT and SAT reflect metabolic status.

The association between reproductive history and abdominal adipose tissue among postmenopausal women: results from the Women's Health Initiative.

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients.

BACKGROUND: In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS: This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS: The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.

Automated Deep Learning-Based Segmentation of Abdominal Adipose Tissue on Dixon MRI in Adolescents: A Prospective Population-Based Study.

BACKGROUND. The prevalence of childhood obesity has increased significantly worldwide, highlighting a need for accurate noninvasive quantification of body fat distribution in children. OBJECTIVE. The purpose of this study was to develop and test an automated deep learning method for subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) segmentation using Dixon MRI acquisitions in adolescents. METHODS. This study was embedded within the Generation R Study, a prospective population-based cohort study in Rotterdam, The Netherlands. The current study included 2989 children (1432 boys, 1557 girls; mean age, 13.5 years) who underwent investigational whole-body Dixon MRI after reaching the age of 13 years during the follow-up phase of the Generation R Study. A 2D competitive dense fully convolutional neural network model (2D-CDFNet) was trained from scratch to segment abdominal SAT and VAT using Dixon MRI-based images. The model underwent training, validation, and testing in 62, eight, and 15 children, respectively, who were selected by stratified random sampling, with manual segmentations used as reference. Segmentation performance was assessed using the Dice similarity coefficient and volumetric similarity. Two observers independently performed subjective visual assessments of automated segmentations in 504 children, selected by stratified random sampling, with undersegmentation and oversegmentation scored on a scale of 0-3 (with a score of 3 denoting nearly perfect segmentation). For 2820 children for whom complete data were available, Spearman correlation coefficients were computed among MRI measurements and BMI and dual-energy x-ray absorptiometry (DEXA)-based measurements. The model used (gitlab.com/radiology/msk/genr/abdomen/cdfnet) is publicly available. RESULTS. In the test dataset, the mean Dice similarity coefficient and mean volu-metric similarity, respectively, were 0.94 ± 0.03 [SD] and 0.98 ± 0.01 [SD] for SAT and 0.85 ± 0.05 and 0.92 ± 0.04 for VAT. The two observers assigned a score of 3 for SAT in 94% and 93% for the undersegmentation proportion and in 99% and 99% for the oversegmentation proportion, and they assigned a score of 3 for VAT in 99% and 99% for the undersegmentation proportion and in 95% and 97% for the oversegmentation proportion. Correlations with SAT and VAT were 0.808 and 0.698 for BMI and 0.941 and 0.801 for DEXA-derived fat mass. CONCLUSION. We trained and evaluated the 2D-CDFNet model on Dixon MRI in adolescents. Quantitative and qualitative measures of automated SAT and VAT segmentations indicated strong model performance. CLINICAL IMPACT. The automated model may facilitate large-scale studies investigating abdominal fat distribution on MRI among adolescents as well as associations of fat distribution with clinical outcomes.

Automated abdominal adipose tissue segmentation and volume quantification on longitudinal MRI using 3D convolutional neural networks with multi-contrast inputs.

OBJECTIVE: Increased subcutaneous and visceral adipose tissue (SAT/VAT) volume is associated with risk for cardiometabolic diseases. This work aimed to develop and evaluate automated abdominal SAT/VAT segmentation on longitudinal MRI in adults with overweight/obesity using attention-based competitive dense (ACD) 3D U-Net and 3D nnU-Net with full field-of-view volumetric multi-contrast inputs. MATERIALS AND METHODS: 920 adults with overweight/obesity were scanned twice at multiple 3 T MRI scanners and institutions. The first scan was divided into training/validation/testing sets (n = 646/92/182). The second scan from the subjects in the testing set was used to evaluate the generalizability for longitudinal analysis. Segmentation performance was assessed by measuring Dice scores (DICE-SAT, DICE-VAT), false negatives (FN), and false positives (FP). Volume agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: ACD 3D U-Net achieved rapid (< 4.8 s/subject) segmentation with high DICE-SAT (median ≥ 0.994) and DICE-VAT (median ≥ 0.976), small FN (median ≤ 0.7%), and FP (median ≤ 1.1%). 3D nnU-Net yielded rapid (< 2.5 s/subject) segmentation with similar DICE-SAT (median ≥ 0.992), DICE-VAT (median ≥ 0.979), FN (median ≤ 1.1%) and FP (median ≤ 1.2%). Both models yielded excellent agreement in SAT/VAT volume versus reference measurements (ICC > 0.997) in longitudinal analysis. DISCUSSION: ACD 3D U-Net and 3D nnU-Net can be automated tools to quantify abdominal SAT/VAT volume rapidly, accurately, and longitudinally in adults with overweight/obesity.

Cold Ambient Temperature Does Not Alter Subcutaneous Abdominal Adipose Tissue Lipolysis and Blood Flow in Endurance-Trained Cyclists.

This study sought to investigate the effect of cold ambient temperature on subcutaneous abdominal adipose tissue (SCAAT) lipolysis and blood flow during steady-state endurance exercise in endurance-trained cyclists. Ten males (age: 23 ± 3 years; peak oxygen consumption: 60.60 ± 4.84 ml·kg-1·min-1; body fat: 18.4% ± 3.5%) participated in baseline lactate threshold (LT) and peak oxygen consumption testing, two familiarization trials, and two experimental trials. Experimental trials consisted of cycling in COLD (3 °C; 42% relative humidity) and neutral (NEU; 19 °C; 39% relative humidity) temperatures. Exercise consisted of 25 min cycling at 70% LT and 25 min at 90% LT. In situ SCAAT lipolysis and blood flow were measured via microdialysis. Heart rate, core temperature, carbohydrate and fat oxidation, blood glucose, and blood lactate were also measured. Heart rate, core temperature, oxygen consumption, and blood lactate increased with exercise but were not different between COLD and NEU. SCAAT blood flow did not change from rest to exercise or between COLD and NEU. Interstitial glycerol increased during exercise (p < .001) with no difference between COLD and NEU. Fat oxidation increased (p < .001) at the onset of exercise and remained elevated thereafter with no difference between COLD and NEU. Carbohydrate oxidation increased with increasing exercise intensity and was greater at 70% LT in COLD compared to NEU (p = .030). No differences were observed between conditions for any other variable. Cycling exercise increased SCAAT lipolysis but not blood flow. Ambient temperature did not alter SCAAT metabolism, SCAAT blood flow, or fat oxidation in well-trained cyclists, though cold exposure increased whole-body carbohydrate oxidation at lower exercise intensities.

Effect of abdominal adipose tissue glucose uptake on brain aging.

INTRODUCTION: Abdominal adipose tissue (AT) mass has adverse effects on the brain. This study aimed to investigate the effect of glucose uptake by abdominal AT on brain aging. METHODS: Three-hundred twenty-five participants underwent total-body positron emission tomography scan. Brain age was estimated in an independent test set (n = 98) using a support vector regression model that was built using a training set (n = 227). Effects of abdominal subcutaneous and visceral AT (SAT/VAT) glucose uptake on brain age delta were evaluated using linear regression. RESULTS: Higher VAT glucose uptake was linked to negative brain age delta across all subgroups. Higher SAT glucose uptake was associated with negative brain age delta in lean individuals. In contrast, increased SAT glucose uptake demonstrated positive trends with brain age delta in female and overweight/obese participants. DISCUSSION: Increased glucose uptake of the abdominal VAT has positive influences on the brain, while SAT may not have such influences, except for lean individuals. HIGHLIGHTS: Higher glucose uptake of the visceral adipose tissue was linked to decelerated brain aging. Higher glucose uptake of the subcutaneous adipose tissue (SAT) was associated with negative brain age delta in lean individuals. Faster brain aging was associated with increased glucose uptake of the SAT in female and overweight and obese individuals.

Comprehensive analysis of changes in expression of lncRNA, microRNA and mRNA in liver tissues of chickens with high or low abdominal fat deposition.

1. The liver of chickens is a dominant lipid biosynthetic tissue and plays a vital role in fat deposition, particularly in the abdomen. To determine the molecular mechanisms involved in its lipid metabolism, the livers of chickens with high (H) or low (L) abdominal fat content were sampled and sequencing on long non-coding RNA (lncRNA), messenger RNA (mRNA) and small RNA (microRNA) was performed.2. In total, 351 expressed protein-coding genes for long non-coding RNA (DEL; 201 upregulated and 150 downregulated), 400 differentially expressed genes (DEG; 223 upregulated and 177 downregulated) and 10 differentially expressed miRNA (DEM; four upregulated and six downregulated) were identified between the two groups. Multiple potential signalling pathways related to lipogenesis and lipid metabolism were identified via pathway enrichment analysis. In addition, 173 lncRNA - miRNA - mRNA interaction regulatory networks were identified, including 30 lncRNA, 27 mRNA and seven miRNA.3. These networks may help regulate lipid metabolism and fat deposition. Five promising candidate genes and two lncRNA may play important roles in the regulation of adipogenesis and lipid metabolism in chickens.

Effect of sex-specific abdominal fat tissue composition on WHO/ISUP nuclear grade of clear cell renal cell carcinoma.

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

The use of portable abdominal bioimpedance analyzer Yscope in the assessment of abdominal obesity.

BACKGROUND: Obesity, especially abdominal obesity, is strongly correlated with metabolic and other health risks. Diagnosis and assessment of obesity is important in clinical and routine preventive practice. From the point of view of risk, it is necessary to distinguish not only the area of fat tissue accumulation, but also its type. OBJECTIVE: The aim of the study was to use a new portable abdominal bioimpedance analyzer, which is intended for the area of abdominal adipose tissue, as part of the evaluation of the body structure of a selected group of volunteers with a focus on the differentiation of subcutaneous and visceral adipose tissue and to assess its usefulness in practice. MATERIAL AND METHODS: Body composition was analyzed using a portable abdominal bioimpedance analyzer Yscope (PA-BIA) in combination with a bioimpedance device InBody 970 (high-frequency bioelectrical impedance/HF-BIA). Eighty-three volunteers at the age of 24.92±7.24 years with representation of both sexes participated in the study. RESULTS: Abdominal fat did not differ significantly between the sexes, women reached an average value of 2.01±1.14 kg, men 2.22±1.60 kg (p>0.05). Gender differentiation was manifested in the case of visceral fat (p<0.01) and visceral fat area (p<0.01), the values of which were lower in women than in men. In the case of subcutaneous fat, we found the opposite trend of values in relation to gender, where lower values were achieved by men, but there were no significant differences (p>0.05). Visceral fat was most correlated with abdominal fat (r=0.86) and waist circumference (r=0.85), subcutaneous fat had the strongest positive correlations with abdominal fat (r=0.93) and with body fat mass (r=0.93). CONCLUSIONS: PA-BIA in combination with HF-BIA makes it possible to determine the representation of subcutaneous and visceral fat in the abdominal area, which the conventional MFS-BIA method does not allow. When evaluating body composition, significant gender differentiation is confirmed, which is an important factor affecting different health risks related to gender and the representation of different types of fat tissue localized and accumulated in different parts of the body.

Transcriptome analysis reveals FABP5 as a key player in the development of chicken abdominal fat, regulated by miR-122-5p targeting.

BACKGROUND: The development of abdominal fat and meat quality are closely related and can impact economic efficiency. In this study, we conducted transcriptome sequencing of the abdominal fat tissue of Gushi chickens at 6, 14, 22, and 30 weeks, and selected key miRNA-mRNA regulatory networks related to abdominal fat development through correlation analysis. RESULTS: A total of 1893 differentially expressed genes were identified. Time series analysis indicated that at around 6 weeks, the development of chicken abdominal fat was extensively regulated by the TGF-ß signaling pathway, Wnt signaling pathway, and PPAR signaling pathway. However, at 30 weeks of age, the apoptosis signaling pathway was the most significant, and correlation analysis revealed several genes highly correlated with abdominal fat development, including Fatty Acid Binding Protein 5 (FABP5). Based on miRNA transcriptome data, it was discovered that miR-122-5p is a potential target miRNA for FABP5. Cell experiments showed that miR-122-5p can directly target FABP5 to promote the differentiation of preadipocytes. CONCLUSION: The present study confirms that the key gene FABP5 and its target gene miR-122-5p are critical regulatory factors in the development of chicken abdominal fat. These results provide new insights into the molecular regulatory mechanisms associated with the development of abdomen-al fat in chickens.

Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement. METHODS: Adult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI. RESULTS: Treatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively). CONCLUSIONS: In adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF. CLINICAL TRIAL NUMBER: NCT01265498. IMPACT AND IMPLICATIONS: Although central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

Anthropometric estimators of abdominal fat volume in adults with overweight and obesity.

BACKGROUND/OBJECTIVES: To evaluate anthropometric measures for the prediction of whole-abdominal adipose tissue volumes VXAT (subcutaneous VSAT, visceral VVAT and total VTAT) in patients with obesity. SUBJECTS/METHODS: A total of 181 patients (108 women) with overweight or obesity were analyzed retrospectively. MRI data (1.5 T) were available from independent clinical trials at a single institution (Integrated Research and Treatment Center of Obesity, University of Leipzig). A custom-made software was used for automated tissue segmentation. Anthropometric parameters (AP) were circumferences of the waist (WC) and hip (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and the (hypothetical) hip-to-height ratio (HHtR). Agreement was evaluated by standard deviations sd% of percent differences between estimated volumes (using results of linear AP-VXAT regression) and measured ones as well as Pearson's correlation coefficient r. RESULTS: For SAT volume estimation, the smallest sd% for all patients was seen for HC (25.1%) closely followed by HHtR (25.2%). Sex-specific results for females (17.5% for BMI and 17.2% for HC) and males (20.7% for WC) agreed better. VAT volumes could not be estimated reliably by any of the anthropometric measures considered here. TAT volumes in a mixed population could be best estimated by BMI closely followed by WC (roughly 17.5%). A sex-specific consideration reduced the deviations to around 16% for females (BMI and WC) and below 14% for males (WC). CONCLUSIONS: We suggest the use of sex-specific parameters-BMI or HC for females and WC for males-for the estimation of abdominal SAT and TAT volumes in patients with overweight or obesity.

17ß-hydroxysteroid dehydrogenase type 2 activity, expression and cellular localization in abdominal adipose tissues from women.

CONTEXT: 17ß-hydroxysteroid dehydrogenase type 2 (17ß-HSD2) may be involved in the local modulation of estradiol (E2) availability in adipose tissues. OBJECTIVE: To assess the conversion of E2 into estrone (E1) as well as the expression of 17ß-HSD2 and its localization in omental (OM) and subcutaneous (SC) adipose tissues obtained from women. METHODS: Rates of 14 C-E1 formation from 14 C-E2 were measured in OM and SC adipose tissue homogenates from 29 women. Specific 17ß-HSD2 inhibitor EM-919 was tested in OM and SC adipose tissue homogenates (n = 6). 17ß-HSD2 mRNA expression was measured in whole OM and SC adipose tissues (n = 14). Cellular localization of the enzyme was examined using immunohistochemistry. Anthropometric measurements were obtained and body composition as well as body fat distribution were measured. RESULTS: Significant 14 C-E1 formation from 14 C-E2 in OM and SC tissue homogenates was detected. The rate of 14 C-E1 formation was significantly higher in OM than SC adipose tissue (p < .0001). The conversion of 14 C-E2 to 14 C-E1 was significantly inhibited by EM-919 in OM (p < .05) and SC (p < .05) adipose tissues. Significantly higher expression of 17ß-HSD2 mRNA in OM versus SC fat was found (p = .03). 17ß-HSD2 was localized in the vasculature of OM and SC tissues. Significant negative associations were detected between OM 17ß-HSD2 activity and body mass index, WC, lean body mass as well as SC adipose tissue areas. CONCLUSION: 17ß-HSD2 converts E2 to E1 in OM and SC adipose tissues of women. The activity of this enzyme decreases with increasing adiposity.

Isthmin-1 (ISM1), a novel adipokine that reflects abdominal adipose tissue distribution in individuals with obesity.

BACKGROUND: The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment. METHODS AND RESULTS: A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1's efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways. CONCLUSION: The study's results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks.

Abdominal fat and muscle distributions in different stages of colorectal cancer.

BACKGROUND: The purpose of this study is to explore the difference of abdominal fat and muscle composition, especially subcutaneous and visceral adipose tissue, in different stages of colorectal cancer (CRC). MATERIALS AND METHODS: Patients were divided into 4 groups: healthy controls (patients without colorectal polyp), polyp group (patients with colorectal polyp), cancer group (CRC patients without cachexia), and cachexia group (CRC patients with cachexia). Skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) were assessed at the third lumbar level on computed tomography images obtained within 30 days before colonoscopy or surgery. One-way ANOVA and linear regression were used to analyze the difference of abdominal fat and muscle composition in different stages of CRC. RESULTS: A total of 1513 patients were divided into healthy controls, polyp group, cancer group, and cachexia group, respectively. In the development of CRC from normal mucosa to polyp and cancer, the VAT area of the polyp group was significantly higher than that of the healthy controls both in male (156.32 ± 69.71 cm2 vs. 141.97 ± 79.40 cm2, P = 0.014) and female patients (108.69 ± 53.95 cm2 vs. 96.28 ± 46.70 cm2, P = 0.044). However, no significant differences were observed of SAT area between polyp group and healthy controls in both sexes. SAT area decreased significantly in the male cancer group compared with the polyp group (111.16 ± 46.98 cm2 vs. 126.40 ± 43.52 cm2, P = 0.001), while no such change was observed in female patients. When compared with healthy controls, the SM, IMAT, SAT, and VAT areas of cachexia group was significantly decreased by 9.25 cm2 (95% CI: 5.39-13.11 cm2, P < 0.001), 1.93 cm2 (95% CI: 0.54-3.32 cm2, P = 0.001), 28.84 cm2 (95% CI: 17.84-39.83 cm2, P < 0.001), and 31.31 cm2 (95% CI: 18.12-44.51 cm2, P < 0.001) after adjusting for age and gender. CONCLUSION: Abdominal fat and muscle composition, especially SAT and VAT, was differently distributed in different stages of CRC. It is necessary to pay attention to the different roles of subcutaneous and visceral adipose tissue in the development of CRC.

The E3 ubiquitin ligase Pellino3 protects against obesity-induced inflammation and insulin resistance.

Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1ß (IL-1ß) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced expression of the E3 ubiquitin ligase Pellino3 in human abdominal adipose tissue from obese subjects and in adipose tissue of mice fed a high-fat diet and showing signs of insulin resistance. Pellino3-deficient mice demonstrated exacerbated high-fat-diet-induced inflammation, IL-1ß expression, and insulin resistance. Mechanistically, Pellino3 negatively regulated TNF receptor associated 6 (TRAF6)-mediated ubiquitination and stabilization of hypoxia-inducible factor 1α (HIF1α), resulting in reduced HIF1α-induced expression of IL-1ß. Our studies identify a regulatory mechanism controlling diet-induced insulin resistance by highlighting a critical role for Pellino3 in regulating IL-1ß expression with implications for diseases like type 2 diabetes.

Abdominal fat quantification using convolutional networks.

OBJECTIVES: To present software for automated adipose tissue quantification of abdominal magnetic resonance imaging (MRI) data using fully convolutional networks (FCN) and to evaluate its overall performance-accuracy, reliability, processing effort, and time-in comparison with an interactive reference method. MATERIALS AND METHODS: Single-center data of patients with obesity were analyzed retrospectively with institutional review board approval. Ground truth for subcutaneous (SAT) and visceral adipose tissue (VAT) segmentation was provided by semiautomated region-of-interest (ROI) histogram thresholding of 331 full abdominal image series. Automated analyses were implemented using UNet-based FCN architectures and data augmentation techniques. Cross-validation was performed on hold-out data using standard similarity and error measures. RESULTS: The FCN models reached Dice coefficients of up to 0.954 for SAT and 0.889 for VAT segmentation during cross-validation. Volumetric SAT (VAT) assessment resulted in a Pearson correlation coefficient of 0.999 (0.997), relative bias of 0.7% (0.8%), and standard deviation of 1.2% (3.1%). Intraclass correlation (coefficient of variation) within the same cohort was 0.999 (1.4%) for SAT and 0.996 (3.1%) for VAT. CONCLUSION: The presented methods for automated adipose-tissue quantification showed substantial improvements over common semiautomated approaches (no reader dependence, less effort) and thus provide a promising option for adipose tissue quantification. CLINICAL RELEVANCE STATEMENT: Deep learning techniques will likely enable image-based body composition analyses on a routine basis. The presented fully convolutional network models are well suited for full abdominopelvic adipose tissue quantification in patients with obesity. KEY POINTS: • This work compared the performance of different deep-learning approaches for adipose tissue quantification in patients with obesity. • Supervised deep learning-based methods using fully convolutional networks  were suited best. • Measures of accuracy were equal to or better than the operator-driven approach.

Why Do People Gain Belly Fat in Rural Areas? A Study of Urinary Metal(loid)s and Abdominal Obesity in China.

Obesity is prevalent in rural areas of China, and there are inconsistent findings regarding the association between metal(loid) exposure and the risk of obesity. Abdominal obesity (AOB), which reflects visceral fat abnormity, is a crucial factor in studying obesity-related diseases. We conducted a study measuring 20 urinary metal(loid)s, 13 health indicators, and the waist circumference (WC) in 1849 participants from 10 rural areas of China to investigate their relationships. In the single exposure models, we found that urinary chromium (Cr) was significantly associated with the odds of having AOB [adjusted odds ratio (OR) = 1.81 (95% confidence interval (CI): 1.24, 2.60)]. In the mixture exposure models, urinary Cr consistently emerged as the top contributor to AOB, while the overall effect of mixed metal(loid)s was positive toward the odds of having AOB [adjusted OR: 1.33 (95% CI: 1.00, 1.77)], as revealed from the quantile g-computation model. After adjusting for the effects of other metal(loid)s, we found that the elevation of apolipoprotein B and systolic blood pressure significantly mediated the association between urinary Cr and the odds of having AOB by 9.7 and 19.4%, respectively. Our results suggest that exposure to metal(loid)s is a key factor contributing to the prevalence of AOB and WC gain in rural areas of China.

Correlation between serum uric acid and body fat distribution in patients with MAFLD.

BACKGROUND: Metabolic dysfunction associated with fatty liver disease (MAFLD) is often correlated with obesity and hyperuricemia. The present study aimed to determine the association between serum uric acid (SUA) and central fat distribution in patients with MAFLD. METHODS: A total of 485 patients were classified into the following groups: (1) controls without MAFLD and hyperuricemia (HUA), (2) MAFLD with normal SUA, and (3) MAFLD with HUA. DUALSCAN HDS-2000 was used to measure visceral fat (VAT) and subcutaneous fat (SAT). Dual-energy X-ray absorptiometry (DEXA) was used to measure body fat distribution. RESULTS: MAFLD patients with HUA had remarkably higher BMI, fasting insulin, OGIRT AUC, ALT, AST, TG, VAT, SAT, Adipo-IR, trunk fat mass, android fat, and total body fat than MAFLD patients with normal SUA (all p < 0.05). The increase in VAT, SAT, CAP, Adipo-IR, upper limbs fat mass, trunk fat mass, and android fat, as well as the percentage of MAFLD, were significantly correlated with the increase in SUA. The percentage of MAFLD patients with HUA increased significantly with increasing VAT or SAT, as determined by the Cochran-Armitage trend test (all p < 0.05). Furthermore, VAT (OR = 1.01 CI: 1.00, 1.03; p < 0.05) and adipo-IR (OR = 1.09 CI: 1.00, 1.19; p < 0.05) were associated with circling SUA in MAFLD after adjusting for sex, age, TG, TC, HOMA-IR, and BMI. CONCLUSION: Abdominal fat promotes the co-existence of HUA and MAFLD, while weight loss, especially, decreasing VAT, is of great importance to decrease SUA levels and manage MAFLD.