Baseline Visceral Adipose Tissue Research Articles

Effect of repeated prolonged exercise on liver fat content and visceral adipose tissue in well-trained older men.

Liver fat (LF) and visceral adipose tissue (VAT) content decreases with training, however, this has mainly been investigated in sedentary obese or healthy participants. The aim of this study was to investigate the effects of repeated prolonged exercise on LF and VAT content in well-trained older men and to compare baseline LF and VAT content to recreationally active older men. A group of five well-trained older men were tested before and after cycling a total distance of 2558 km in 16 consecutive days. VAT content and body composition was measured using DXA before a bicycle ergometer test was performed to determine maximal fat oxidation (MFO), maximal oxygen consumption ( ), and the relative intensity at which MFO occurred (Fatmax). LFcontent was measured on a separate day using MRI. For comparison of baseline values, a control group of eight healthy age- and BMI-matched recreationally active men were recruited. The well-trained older men had lower VAT (p = 0.02), and a tendency toward lower LF content (p = 0.06) compared with the control group. The intervention resulted in decreased LF content (p = 0.02), but VAT, fat mass, and lean mass remained unchanged. , MFO, and Fatmax were not affected by the intervention. The study found that repeated prolonged exercise reduced LF content, but VAT and remained unchanged. Aerobic capacity was aligned with lower LF and VAT in older active men.

Characterization of Anthropometric Changes in Patients with Relapsed/Refractory Myeloma Treated with BCMA Bispecific Antibody Teclistamab

Introduction: Cancer-associated cachexia is associated with poor survival rates in several cancer types. Multiple Myeloma (MM) preferentially occurs in the elderly and is the most common cancer that causes lytic bone metastasis causing bone pain, fractures, mobility limitations, and falls. Cachexia is projected to be common in myeloma but has not been fully studied. Myeloma treatments including corticosteroids, radiation and alkylators cause muscle loss, while novel immunotherapy is tumor-specific but their impact on cachexia is unknown. We characterize the changes in body composition in patients with relapsed/refractory myeloma treated with BCMA bispecific antibody teclistamab and determine the association between body composition with treatement response and overall survival. Methods: 49 MM patients treated with teclistamab between 2000 and 2021 were included. All were with relapsed/refractory disease after > 4 lines of therapy and received an approved dose and schedule of teclistamab. The response assessment was according to IMWG criteria. Body weight, body mass index (BMI), tumor burden, and organ function were assessed at baseline and post-treatment. Standard-of-care abdominopelvic CT or PET/CT scans at baseline and at last known follow up were analyzed with Data Analysis Facilitation Suite (DAFS) software to quantify skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Differences between groups were tested using the χ 2 test or paired t-test. Progression free survival (PFS) and overall survival (OS) from the start of teclistamab to progression and death or last follow-up, respectively, were analyzed by the Kaplan-Meier method. Comparisons were made with the log-rank test. Results: Patient characteristics are detailed in Table 1. Based on the WHO definition, 2% were underweight, 16% were normal weight, 19% were overweight and 13% were obese, at baseline. The baseline mean SKM was 105.6 ± 27.8 (Male 122.0 ± 25.3, female 93.4 ± 23.5). SAT and VAT varied widely. Median SAT was 196.5 (range 48.3-558.6), and median VAT was 136.6 (33.09-448.1). Of 32 patients in the obese group, 16 (50%) patients had SKM that was below the mean SKM of the group. Baseline SAT and VAT, but not SKM were correlated with BMI. Twenty-seven of the 49 patients had paired imaging. The absolute changes in skeletal muscle and adipose tissue compartments are shown in Table 2. A majority of patients had a decline in SKM, SAT and VAT post-treatment: mean SKM decrease was 8.9 cm 2 ( p ≤ 0.01), mean SAT decreased 24.3 cm 2 ( p = 0.02) and mean VAT decreased 27.4 cm 2 ( p = 0.03), while BMI and weight were unchanged. Nineteen of 27 (70%) subjects responded to therapy. The changes in SKM, VAT, and SAT loss did not differ significantly between responders and non-responders. 38.8% of patients (19/49) had died by the end of the follow-up. Median follow-up duration was 2.8 years, overall survival was 1.7 years and PFS was 0.9 years. Baseline SKM, SAT, and VAT did not correlate with PFS or OS, but a decline in SMK significantly correlated with a shorter OS (p=0.04); 7/18 patients with decreased SKM and 2/9 patients with unchanged or increased SKM died. Response correlated strongly with overall survival (p=0.002). Conclusions: Body composition analysis of standard CT images may provide clinically relevant information for patients with advanced myeloma. Sarcopenia was common despite high BMI, and a further decline in skeletal muscle mass correlated with shorter survival, regardless of response to tumor-specific immunotherapy. Anthropometric changes should be validated in larger patient cohorts and included in future clinical trials. Further efforts should focus on the maintenance of muscle and visceral adipose tissue in this patient population.

Dual-Energy X-Ray Absorptiometry Derived Adiposity Measures and Pre-Frailty/Frailty among Norwegian Adults: The Tromsø Study 2007–2015

ObjectivesAging is associated with changes in body composition. Excess adiposity among older adults has been linked with metabolic syndromes and aggravated age-associated decline in physical functioning. Few longitudinal studies have explored the association between dual-energy X-ray absorptiometry (DXA)-derived total as well as central adiposity measures and frailty. We examined the association of DXA-derived total and central adiposity with pre-frailty/frailty among Norwegian adults after 8 years of follow-up.DesignProspective observational study.SettingCommunity-dwelling adults from Tromsø, Norway.MeasurementsAdiposity was defined by fat mass index (FMI) and visceral adipose tissue (VAT) mass assessed using DXA measures. Frailty status was assessed by low grip strength, slow walking speed, exhaustion, unintentional weight loss and low physical activity level. Pre-frail and frail participants at baseline were excluded. Sex-stratified multivariable logistic regression models were used to investigate the association.ResultsParticipants comprised 234 women (mean age 68 years) and 146 men (mean age 69 years) attending the population-based Tromsø Study in 2007–2008 (Tromsø6) and 2015–2016 (Tromsø7). At the end of follow-up, 25.6% of the women and 27.4% of the men were pre-frail/frail. Compared with women in the lowest tertiles, those in the highest tertile of baseline FMI (odds ratio [OR] 4.42, 95% confidence interval [CI] 1.88–10.35) and VAT mass (OR 2.47, 95% CI 1.10–5.50), respectively had higher odds for pre-frailty/frailty at follow-up.ConclusionWe found a higher likelihood of pre-frailty/frailty in later years among women with general and central adiposity in adulthood, highlighting the importance of preventing excess adiposity for healthy aging.

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.

Longitudinal Changes in Adiposity and Lower Urinary Tract Symptoms Among Older Men.

Adiposity increases risk for male lower urinary tract symptoms (LUTS), although longitudinal studies have produced conflicting results. No prior studies have evaluated longitudinal associations of changes in adiposity with concurrent LUTS severity among older men. We used repeated adiposity measurements from dual-energy x-ray absorptiometry (DXA), body mass index (BMI), and American Urological Association Symptom Index (AUASI) measured at 4 study visits over a 9-year period among 5 949 men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Linear mixed effect models adjusted for age, health-related behaviors, and comorbidities were created to evaluate the association between baseline and change in visceral adipose tissue (VAT) area, total fat mass, and BMI with change in LUTS severity measured by the AUASI. A nonlinear association was observed between baseline VAT area and change in AUASI: men in baseline VAT tertile (T) 2 had a lower annual increase in AUASI score compared to men in T1 and T3 (T2 vs T1: β = -0.07; 95% CI -0.12, -0.03; p = .008; T3 vs T1: NS) but differences were small. No significant associations were observed between change in VAT area and change in AUASI score. Neither baseline tertiles nor change in total fat mass or BMI were associated with change in AUASI score. Changes in VAT area, total fat mass, and BMI were not associated with change in LUTS severity in this cohort. Thus, despite other health benefits, interventions targeting adiposity alone are unlikely to be effective for preventing or treating LUTS among older men.

A neurobiological link between transportation noise exposure and metabolic disease in humans

BackgroundChronic transportation noise exposure associates with cardiovascular events through a link involving heightened stress-associated neurobiological activity (as amygdalar metabolic activity, AmygA) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). Increased AmygA also associates with greater visceral adipose tissue (VAT) and type 2 diabetes mellitus (DM). While relationships between noise exposure and VAT and DM have been reported, the underlying mechanisms remain incompletely understood. We tested whether: (1) transportation noise exposure associates with greater (a) baseline and gains in VAT and (b) DM risk, and (2) heightened AmygA partially mediates the link between noise exposure and these metabolic diseases. MethodsVAT was measured in a retrospective cohort (N = 403) who underwent clinical 18F-FDG-PET/CT. AmygA was measured in those with brain imaging (N = 238). Follow-up VAT was remeasured on available imaging (N = 67). Among individuals (N = 224) without baseline DM, incident DM was adjudicated over 2 years from clinical records. Noise (24-h average) was modeled at each individual’s home address. Linear regression, survival, and mediation analyses were employed. ResultsHigher noise exposure (upper tertile vs. others) associated with greater: baseline VAT (standardized β [95% confidence interval (CI)]= 0.230 [0.021, 0.438], p = 0.031), gains in VAT (0.686 [0.185, 1.187], p = 0.008 adjusted for baseline VAT), and DM (hazard ratio [95% CI]=2.429 [1.031, 5.719], p = 0.042). The paths of: ↑noise exposure→↑AmygA→↑baseline VAT and ↑noise exposure→↑AmygA→↑subsequent DM were significant (p < 0.05). ConclusionsIncreased transportation noise exposure associates with greater VAT and DM. This relationship is partially mediated by stress-associated neurobiological activity. These findings suggest altered neurobiology contributes to noise exposure’s link to metabolic diseases.

Association of Visceral Adipose Tissue and Insulin Resistance with Incident Metabolic Syndrome Independent of Obesity Status: The IRAS Family Study.

Although increasing evidence suggests that visceral adipose tissue (VAT) is a major underlying cause of metabolic syndrome (MetS), few studies have measured VAT at multiple time points in diverse populations. VAT and insulin resistance were hypothesized to differ by MetS status within BMI category in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study and, further, that baseline VAT and insulin resistance and increases over time are associated with incident MetS. Generalized estimating equations were used for differences in body fat distribution and insulin resistance by MetS status. Mixed effects logistic regression was used for the association of baseline and change in adiposity and insulin resistance with incident MetS across 5 years, adjusted for age, sex, race/ethnicity, and family correlation. VAT and insulin sensitivity differed significantly by MetS status and BMI category at baseline. VAT and homeostatic model assessment of insulin resistance (HOMA-IR) at baseline (VAT odds ratio [OR] = 1.16 [95% CI: 1.12-2.31]; HOMA-IR OR = 1.85 [95% CI: 1.32-2.58]) and increases over time (VAT OR = 1.55 [95% CI: 1.22-1.98]; HOMA-IR OR = 3.23 [95% CI: 2.20-4.73]) were associated with incident MetS independent of BMI category. Differing levels of VAT may be driving metabolic heterogeneity within BMI categories. Both overall and abdominal obesity (VAT) may play a role in the development of MetS. Increased VAT over time contributed additional risk.

Increases in DXA-Derived Visceral Fat Across One Season in Professional Rugby Union Players: Importance of Visceral Fat Monitoring in Athlete Body Composition Assessment

Introduction: In rugby, the average player body mass has increased by approximately 25% since 1955. Visceral adipose tissue (VAT) is associated with low grade inflammation, and chronic diseases, such as cardiovascular diseases. The purpose of this study was to investigate changes in VAT in relation to other indices of body composition, across 1 season in professional rugby. Methodology: One hundred and sixteen male rugby union players’ (age: 26.2 ± 4.6 y, BMI: 29.40 ± 3.22 kg.m2) total body composition dual energy X-ray absorptiometry scans from 4 time points across the season (baseline, preseason, midseason, and postseason) were analyzed. Players were grouped by playing position, forwards (n = 65) and backs (n = 51). Players followed individually tailored diet plans. Results: Mean baseline VAT was 404.67 ± 229.43 g (forwards: 469.36 ± 263.16 g, backs: 311.40 ± 121.15 g). Total mass, lean mass, body fat percentage (%BF), and VAT were greater in forwards than backs at all 4 timepoints. Meaningful increases in VAT across the season, were observed in 37.5% of backs and 53.6% of forwards. There was a positive linear relationship between lean mass and total mass, up to 116.04 kg total mass. Beyond this threshold, lean mass accumulation reduced and %BF and VAT mass increased. There were significant relationships between %BF, VAT, and BMI (p < 0.001), but no physiological relevant pattern was discerned. Conclusions: Despite regular high-intensive exercise and individually tailored dietary control across a professional rugby season, players from both playing positions demonstrated increases in VAT, although the cause remains unknown. Our findings indicate the importance of monitoring VAT in athletes alongside standard measures of body composition. Additionally, our findings suggest there may be an upper threshold of body mass beyond which lean mass may not increase further and instead %BF and VAT are more likely to accumulate. Further research is required to identify how increasing player size may impact long-term cardiometabolic health given the known links between VAT and cardiometabolic risk.

Effects of Empagliflozin Treatment on Glycerol-Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial.

The aim of this study was to determine the effects of empagliflozin on glycerol-derived hepatic gluconeogenesis in adults with obesity without type 2 diabetes mellitus (T2DM) using oral carbon 13 (13 C)-labeled glycerol. A randomized, double-blind, placebo-controlled trial was performedin participants with magnetic resonance imaging assessment of body fat and measurement of glycerol-derived 13 C enrichment in plasma glucose by nuclear magnetic resonance spectroscopy following ingestion of [U-13 C3 ]glycerol. Participants were randomized to oral empagliflozin 10 mg once daily or placebo for 3 months. Glycerol-derived 13 C enrichment studies were repeated, and treatment differences in the mean percentage of 13 C glycerol enrichment in glucose were compared using mixed linear models. Thirty-five participants completed the study. Empagliflozin increased glycerol-derived 13 C enrichment between baseline and follow-up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). No difference was found with placebo. Glycerol-derived 13 C enrichment was lower in participants with high VAT compared with low VAT by 12.6% (P = 0.04), but there was no heterogeneity of the treatment effect by baseline VAT. Glycerol-derived 13 C enrichment was inversely correlated with VAT but was not correlated with weight loss. VAT is associated with endogenous glycerol-derived hepatic gluconeogenesis, and empagliflozin reduces endogenous glycerol gluconeogenesis in adults with obesity without T2DM. These findings suggest a mechanism by which sodium-glucose cotransporter 2 inhibitors may prevent T2DM in obesity.

Abstract 2425: Moderate to vigorous physical activity reduces visceral adipose tissue in obese breast cancer survivors undergoing a weight loss intervention

Abstract Background: Body composition, adipose distribution, and fitness are likely superior to BMI alone in predicting outcomes in obese breast cancer survivors. Visceral adipose tissue (VAT) is thought to be disproportionately responsible for the metabolic and inflammatory changes linking obesity and breast cancer recurrence. Purpose: Feasibility of achievement of high volume moderate-to-vigorous physical activity (MVPA) and its effect on body composition including VAT and other risk biomarkers in older sedentary, obese breast cancer survivors participating in a behavioral weight loss intervention. Methods: Modest caloric restriction (350-500 kcal per day) was combined with a study provided YMCA membership and twice weekly personal trainer sessions. MVPA (40-80% of heart rate reserve in older women) was assessed by Garmin Vivoactive smart watches linked to GarminConnect. Total activity was escalated from 100 minutes week 1 to a total of 300 minutes per week by week 9 with a goal of &amp;gt; 200 min/wk as MVPA. Women were evaluated pre- and post-intervention for peak oxygen consumption (VO2peak), body composition by dual energy x-ray absorptiometry (GE Lunar iDXA), and serum levels of adipokines, cytokines, and hormones. Results: 18 breast cancer survivors were enrolled and completed the 3 months of the behavioral weight loss intervention which included the YMCA membership and twice weekly personal trainer. Median age was 60, 11 had received prior chemotherapy, and 13 were currently taking aromatase inhibitors. Median (and range) baseline anthropomorphic values were BMI 37 (31-43) kg/m2, total mass 95 (76-125) kg, total fat 46 (34-66) kg, and VAT 1.7 (1.0-3.0) kg. All but one had a baseline VAT &amp;gt; 1.17 kg, consistent with elevated risk of metabolic syndrome. 17/18 achieved at least 150 min/wk of MVPA, with a median of 176 (range 55-291) min/wk for weeks 9-12. Fitness measured as VO2peak increased from 18.9 (13.7-25.3) to 21.1 (17.1-31.4) ml/kg/min (p=0.0003; Wilcoxon signed rank test). At 3 months, significant reductions were observed for total mass (median 7%), fat mass (median 13%), and VAT (median 20%, range 1-41%)(p&amp;lt;0.0003); as well as serum leptin, insulin, and leptin: adiponectin ratio (p&amp;lt;0.01). A strong correlation was observed between week 9-12 MVPA and leptin: adiponectin ratio (p=0.001) with more modest correlations between week 9-12 MVPA and VAT loss (p=0.043), and leptin: adiponectin ratio and VAT loss (p=0.013). Conclusion: High volume moderate-to-vigorous physical activity can be achieved by older, sedentary, obese breast cancer survivors; and this translates to favorable modulation of body composition including VAT measures and serum risk biomarkers. Citation Format: Carol J. Fabian, Jennifer R. Klemp, Jeffrey M. Burns, Eric D. Vidoni, Lauren Nye, Christie A. Befort, Jill M. Hamilton-Reeves, Debra K. Sullivan, Teresa A. Phillips, Stephen D. Hursting, Bruce F. Kimler. Moderate to vigorous physical activity reduces visceral adipose tissue in obese breast cancer survivors undergoing a weight loss intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2425.

EXERCISE TRAINING COULD REDUCE INFLAMMATORY ACTIVITY OF VISCERAL ADIPOSE TISSUE IN OVERWEIGHT WOMEN

Objective: Visceral adipose tissue (VAT) plays pivotal roles for an increased risk of cardiometabolic disease through triggering inflammatory process. This prospective study aimed to evaluate whether the exercise training could reduce inflammatory activity of VAT assessed by F-18 fluorodeoxyglucoase (FDG) positron emission tomography-computerized tomography (PET/CT). Design and method: Twenty-three overweight women who participated in exercise training program were included. Exercise training program was composed of aerobic exercise (45 min/session, 300 Kcal/day) and muscle strength training (20 min/session, 100 Kcal/day) 5 times per week for 3 months. They underwent F-18 FDG PET/CT before starting exercise program (baseline) and after completion of 3 months exercise program. Anthropometric data, clinical laboratory data, VAT area, and maximum standardized uptake value (SUVmax) of VAT were compared between baseline and after completion of the total exercise program. Results: Baseline VAT SUVmax showed significant correlation with body weight, body mass index (BMI), waist circumference, and hip circumference. VAT SUVmax was significantly reduced by exercise training program. Exercise training program also reduced body weight, BMI, waist circumference, hip circumference, VAT area, subcutaneous adipose tissue area and blood pressure. The change of VAT SUVmax was significantly higher than the change of VAT area. Conclusions: Exercise training could reduce the inflammatory activity of VAT assessed by F-18 FDG PET/CT. Thus, exercise would be a promising non-pharmacological strategy to reduce inflammatory activity of VAT. Furthermore, F-18 FDG PET/CT could be useful to evaluate the effect of therapeutic intervention targeted to inflammatory VAT activity.

A Novel Hybrid Model for Visceral Adipose Tissue Prediction using Shape Descriptors.

Obesity is gaining increasing attention in modern society since it is associated with various health issues. The visceral adipose tissue (VAT) deposits around the abdominal organs and is considered an extremely important indicator of health risk. VAT can be assessed through magnetic resonance imaging (MRI) or computed tomography (CT) accurately, but the cost is prohibitive. Shape-based body composition prediction has become a promising topic thanks to the prevalence of commodity optical body scan systems, from which numerous anthropometries can be extracted automatically. In this paper, we propose an innovative shape-based hybrid VAT prediction model. The most appealing benefit of our method is to robustly handle the lack of knowledge about gender and demographics. First, we train a baseline VAT prediction model for each gender separately. Second, we train a classifier to predict the gender likelihood and a classifier to predict the shape likelihood of being overestimated in VAT baseline prediction. Third, we integrate the gender likelihood and shape likelihood into the baseline models to derive one hybrid VAT prediction model. We compare our prediction model with other state-of-the-art VAT prediction methods. The result shows that our method outperforms the comparison methods by 21.8% on average.

1624-P: Changes in Childhood Adiposity and Adolescent Testosterone in the EPOCH (Exploring Perinatal Outcomes among Children) Study

Whether changes in visceral adipose tissue (VAT) in childhood predict adolescent androgens is not known. We examined the longitudinal relationship between MRI-assessed visceral adipose tissue (VAT) in childhood and future testosterone (T) among 418 EPOCH participants (209 girls and 209 boys) who were, on average 10.5 years at visit 1 and 16.7 years at visit 2. We used reverse Cox proportional hazards models in which hazard ratios less than 1 indicate greater risk for low (undetectable) sex hormones consistent with pre-puberty. Models explored the associations of baseline VAT, and change in VAT from visit 1 to visit 2, with risk of low sex hormone levels at visit 2, adjusted for covariates selected through backwards regression (race, self-reported Tanner stage, maternal income, insulin and leptin levels). All analyses were stratified by sex. In addition, due to different patterns of fat deposition in white and non-white adults, we tested for effect modification by race. In boys, the association between VAT at visit 1 and T at visit 2 differed by race; more VAT at visit 1 was associated with lower risk of low T at visit 2 among non-white boys (HR 1.02, 95% CI 1.007, 1.04) but not white boys (HR 1.00, 95% CI 0.98, 1.01). In contrast, greater fat accumulation between visits was associated with higher risk of low T at visit 2 (HR 0.90, 95% CI 0.83, 0.96), independent of race and other covariates. Among girls, neither baseline VAT levels, nor VAT accumulation between visits predicted risk of later low T concentrations. We conclude that greater VAT accumulation in childhood is associated with increased risk for low T levels, suggesting delayed puberty, in boys. These associations suggest that fat deposition may influence sex hormone profiles even in early childhood. Disclosure C. Kim: None. K.K. Harrall: None. D.H. Glueck: None. D. Dabelea: None. Funding National Institutes of Health

Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults.

Accumulating evidence linking trimethylamine N-oxide (TMAO) to cardiovascular disease (CVD) risk has prompted interest in developing therapeutic strategies to reduce its production. We compared two lifestyle intervention approaches: hypocaloric versus eucaloric diet, combined with exercise, on TMAO levels in relation to CVD risk factors. Sixteen obese adults (66.1 ± 4.4 years, BMI (body mass index): 35.9 ± 5.3 kg/m2, fasting glucose: 106 ± 16 mg/dL, 2-h PPG (postprandial glucose): 168 ± 37 mg/dL) were randomly assigned to 12 weeks of exercise (5 days/week, 80–85% HRmax (maximal heart rate)) plus either a hypocaloric (HYPO) (−500 kcal) or a eucaloric (EU) diet. Outcomes included plasma TMAO, glucose metabolism (oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamps for glucose disposal rates (GDR)), exercise capacity (VO2max, maximal oxygen consumption), abdominal adiposity (computed tomography scans), cholesterol, and triglycerides. Results showed that body composition (body weight, subcutaneous adiposity), insulin sensitivity, VO2max, and cholesterol all improved (p < 0.05). HYPO decreased the percentage change in TMAO compared to an increase after EU (HYPO: −31 ± 0.4% vs. EU: 32 ± 0.6%, p = 0.04). Absolute TMAO levels were not impacted (HYPO: p = 0.09 or EU: p = 0.53 group). The change in TMAO after intervention was inversely correlated with baseline visceral adipose tissue (r = −0.63, p = 0.009) and GDR (r = 0.58, p = 0.002). A hypocaloric diet and exercise approach appears to be effective in reducing TMAO. Larger trials are needed to support this observation.

Amygdalar Metabolic Activity Independently Associates With Progression of Visceral Adiposity.

Epidemiologic data link psychological stress to adiposity. The underlying mechanisms remain uncertain. To test whether (i) higher activity of the amygdala, a neural center involved in the response to stress, associates with greater visceral adipose tissue (VAT) volumes and (ii) this association is mediated by increased bone marrow activity. Massachusetts General Hospital, Boston, Massachusetts. Two hundred forty-six patients without active oncologic, cardiovascular, or inflammatory disease who underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging were studied. VAT imaging was repeated ∼1 year later in 68 subjects. Metabolic activity of the amygdala (AmygA), hematopoietic tissue activity, and adiposity volumes were measured with validated methods. The relationship between AmygA and baseline and follow-up VAT. AmygA associated with baseline body mass index (standardized β = 0.15; P = 0.01), VAT (0.19; P = 0.002), and VAT/subcutaneous adipose tissue ratio (0.20; P = 0.002), all remaining significant after adjustment for age and sex. AmygA also associated with bone marrow activity (0.15; P = 0.01), which in turn associated with VAT (0.34; P < 0.001). Furthermore, path analysis showed that 48% of the relationship between AmygA and baseline VAT was mediated by increased bone marrow activity (P = 0.007). Moreover, AmygA associated with achieved VAT after 1 year (P = 0.02) after adjusting for age, sex, and baseline VAT. These results suggest a neurobiological pathway involving the amygdala and bone marrow linking psychosocial stress to adiposity in humans. Future studies should test whether targeting this mechanism attenuates adiposity and its complications.

Abdominal fat depots, insulin resistance, and incident diabetes mellitus in women with and without HIV infection.

The aim of this study was to determine the associations between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) mass with homeostatic model assessment-insulin resistance (HOMA-IR) and incidence of diabetes mellitus in women with and without HIV infection. Cross-sectional design for associations between abdominal fat and HOMA-IR; longitudinal design for associations between abdominal fat and incident diabetes. We assessed associations between dual X-ray absorptiometry scan-derived VAT and SAT with HOMA-IR in a subsample from the Women's Interagency HIV Study (n = 226 with and n = 100 without HIV) using linear regression. We evaluated associations of VAT, SAT and HOMA-IR with incident diabetes mellitus using Cox proportional hazards models. VAT mass was positively associated with log HOMA-IR in fully adjusted linear regression models stratified by HIV serostatus, including adjustment for SAT. During median follow-up of 10.6 years, incidence of diabetes was 1.63 [95% confidence interval (95% CI) 1.15-2.31] and 1.32 [95% CI 0.77-2.28] cases per 100 person-years in women with and without HIV (P = 0.52). In a fully adjusted model, baseline VAT (hazard ratio 2.64 per kg; 95% CI 1.14-6.12; P = 0.023) and SAT (hazard ratio 1.34 per kg; 95% CI 0.73-2.45; P = 0.35) were associated with incident diabetes, but the latter was not statistically significant. VAT mass was independently associated with HOMA-IR in women with and without HIV and was independently associated with future development of diabetes.

Effects of a Randomized Weight Loss Intervention Trial in Obese Adolescents on Tibia and Radius Bone Geometry and Volumetric Density.

Obese adolescents have increased fracture risk, but effects of alterations in adiposity on bone accrual and strength in obese adolescents are not understood. We evaluated 12-month changes in trabecular and cortical volumetric bone mineral density (vBMD) and cortical geometry in obese adolescents undergoing a randomized weight management program, and investigated the effect of body composition changes on bone outcomes. Peripheral quantitative computed tomography (pQCT) of the radius and tibia, and whole-body dual-energy X-ray absorptiometry (DXA) scans were obtained at baseline, 6 months, and 12 months in 91 obese adolescents randomized to standard care versus behavioral intervention for weight loss. Longitudinal models assessed effects of body composition changes on bone outcomes, adjusted for age, bone length, and African-American ancestry, and stratified by sex. Secondary analyses included adjustment for physical activity, maturation, vitamin D, and inflammatory biomarkers. Baseline body mass index (BMI) was similar between intervention groups. Twelve-month change in BMI in the standard care group was 1.0 kg/m2 versus -0.4 kg/m2 in the behavioral intervention group (p < 0.01). Intervention groups were similar in bone outcomes, so they were combined for subsequent analyses. For the tibia, BMI change was not associated with change in vBMD or structure. Greater baseline lean body mass index (LBMI) associated with higher cortical vBMD in males, trabecular vBMD in females, and polar section modulus (pZ) and periosteal circumference (Peri-C) in both sexes. In females, change in LBMI positively associated with gains in pZ and Peri-C. Baseline visceral adipose tissue (VFAT) was inversely associated with pZ in males and cortical vBMD in females. Change in VFAT did not affect bone outcomes. For the radius, BMI and LBMI changes positively associated with pZ in males. Thus, in obese adolescents, weight loss intervention with modest changes in BMI was not detrimental to radius or tibia bone strength, and changes in lean, but not adiposity, measures were beneficial to bone development. © 2017 American Society for Bone and Mineral Research.

Greater visceral abdominal fat is associated with a lower probability of conversion of prehypertension to normotension

Prehypertension is associated with increased risk for incident hypertension. However, little is known about how frequently prehypertension converts to normotension, and which variables predict this conversion. We identified 186 Japanese Americans with prehypertension (110 men, 76 women) aged 34-75 years (mean age of 52.3 years) who were followed at 5 and 10 years after enrollment. Blood pressure was measured with a mercury sphygmomanometer and average blood pressure was calculated. Subcutaneous adipose tissue, visceral adipose tissue (VAT), and subcutaneous thigh adipose tissue area were measured by computed tomography. Approximately one-third of those with prehypertension converted to normotension over 10 years of follow-up. Those who converted to normotension were younger, less obese, and had significantly lower baseline SBP, fasting glucose, cholesterol levels, and homeostasis model assessment insulin resistance compared with study participants who continued to have prehypertension or progressed to hypertension. With regard to body fat compartments, study participants with conversion to normotension showed a significantly smaller VAT area compared with the nonconversion group (P < 0.001); but, subcutaneous adipose tissue and subcutaneous thigh adipose tissue were not significant. In multivariate logistic regression analysis, baseline VAT was inversely associated with the conversion independent of age, sex, waist circumference, diabetes, fasting glucose, homeostasis model assessment insulin resistance, non-high-density lipoprotein cholesterol, and SBP [odds ratio per 1 SD VAT increment (95% confidence interval), 0.35 (0.15-0.80), P = 0.012]. This is the first prospective study showing the role of body fat distribution, determined by computed tomography scan, in predicting the natural history of prehypertension. Baseline VAT was inversely and independently associated with the conversion to normal blood pressure. No other adipose variable was significant. The mechanisms responsible for these observations remain to be elucidated.

Increased Visceral Adipose Tissue Is an Independent Predictor for Future Development of Atherogenic Dyslipidemia.

Atherogenic dyslipidemia is frequently observed in persons with a greater amount of visceral adipose tissue (VAT). However, it is still uncertain whether VAT is independently associated with the future development of atherogenic dyslipidemia. The aim of this study was to determine whether baseline and changes in VAT and subcutaneous adipose tissue (SAT) are associated with future development of atherogenic dyslipidemia independent of baseline lipid levels and standard anthropometric indices. Community-based prospective cohort study with 5 years of follow-up. A total of 452 Japanese Americans (240 men, 212 women), aged 34-75 years were assessed at baseline and after 5 years of follow-up. Abdominal fat areas were measured by computed tomography. Atherogenic dyslipidemia was defined as one or more abnormalities in high-density lipoprotein (HDL) cholesterol, triglycerides, or non-HDL cholesterol levels. Baseline VAT and change in VAT over 5 years were independently associated with log-transformed HDL cholesterol, log-transformed triglyceride, and non-HDL cholesterol after 5 years (standardized β = -0.126, 0.277, and 0.066 for baseline VAT, respectively, and -0.095, 0.223, and 0.090 for change in VAT, respectively). However, baseline and change in SAT were not associated with any future atherogenic lipid level. In multivariate logistic regression analysis, incremental change in VAT (odds ratio [95% confidence interval], 1.73 [1.20-2.48]; P = .003), triglycerides (4.01 [1.72-9.33]; P = .001), HDL cholesterol (0.32 [0.18-0.58]; P < .001), and non-HDL cholesterol (7.58 [4.43-12.95]; P < .001) were significantly associated with the future development of atherogenic dyslipidemia independent of age, sex, diastolic blood pressure, homeostasis model assessment insulin resistance, body mass index (BMI), change in BMI, SAT, and baseline atherogenic lipid levels. Baseline and change in VAT were independent predictors for future development of atherogenic dyslipidemia. However, BMI, waist circumference, and SAT were not associated with future development of atherogenic dyslipidemia.

Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat

BackgroundTesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy.Objectives1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.MethodsData were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models.ResultsMetabolic syndrome (MetS-IDF or MetS-NCEP) and FRS were significantly associated with VAT at baseline. Presence of metabolic syndrome ([MetS-NCEP), triglyceride levels >1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively). No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI) and baseline VAT (95% confidence interval [CI] 2.03; 7.44).ConclusionsIndividuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo.