Increase In Visceral Adipose Tissue Research Articles

Effect of changes in body composition and sociodemographic factors on colon cancer survival.

296 Background: Muscle mass, muscle quality, and adipose tissue volumes have been shown to affect colon cancer survival. Further research is required to understand how change in body composition during treatment impacts colon cancer outcomes, and how covariables such mental health and socioeconomic status affect this relationship. The aim of this project was to examine how changes in body composition during chemotherapy for colon cancer impact the duration of disease-free survival (DFS) and how sociodemographic covariables (age, sex, social isolation, depression, anxiety, income, community size) influence this relationship. Methods: Computed tomography (CT) scans from the time of diagnosis and the end of chemotherapy were obtained from individuals treated for stage III colon cancer with oxaliplatin at BC Cancer between 2012 and 2016. Whole body tissue volumes were estimated based on CT images at the level of the third lumbar vertebra, analysed using DAFS Express (Voronoi Health Analytics Inc., Vancouver BC). Muscle quantity was measured as skeletal muscle index (SMI), and muscle quality was measured as skeletal muscle density (SMD) and skeletal muscle gauge (SMG). Quantity of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and total adipose tissue (TAT) were also measured. Social isolation, anxiety, and depression symptoms were measured using the validated Psychosocial Screen for Cancer–Revised. Neighbourhood income and community population were estimated using postal codes. Cox proportional hazard models were calculated for the effect of body composition variables on DFS, and interactions with sociodemographic variables. Results: Significant reductions in SMI, SMD, SMG, VAT, IMAT and TAT were observed between diagnosis and post-chemotherapy (n=282). Improved survival was associated with higher SMD and lower IMAT at diagnosis and post-chemotherapy, lower VAT at diagnosis, and an increase in VAT or TAT during chemotherapy. Body composition had a more significant effect on survival in individuals who were older, female, or lived in smaller communities. Conclusions: Significant reductions in SMI, SMD, SMG, VAT, IMAT and TAT were observed between diagnosis and post-chemotherapy (n=282). Improved survival was associated with higher SMD and lower IMAT at diagnosis and post-chemotherapy, lower VAT at diagnosis, and an increase in VAT or TAT during chemotherapy. Body composition had a more significant effect on survival in individuals who were older, female, or lived in smaller communities.

Association between visceral adipose tissue radiodensity and overall survival among older adults with colorectal carcinoma.

43 Background: Central obesity is a known risk factor for colorectal carcinoma (CRC); however, the association between visceral adipose tissue (VAT) and survival outcomes remains unclear. This study aims to investigate the relationship between VAT and overall survival (OS) among older adults with CRC. Methods: We analyzed data from the Cancer and Aging Resilience Evaluation registry, including adults aged ≥ 60 years with newly diagnosed CRC who were seen at the University of Alabama at Birmingham for initial consultation between October 2017 and April 2024. Using single-slice computed tomography staging scans, we calculated visceral adipose tissue radiodensity (VATD; in Hounsfield units, HU) at the third lumbar vertebra (L3) using validated methods. A lower VATD (more negative score) indicates higher visceral adipose tissue. Participants were followed until death or the study cutoff date of July 10, 2024. Kaplan-Meier survival analysis was performed to estimate OS for those with low VAT (VATD ≥ median VATD) versus high VAT (VATD < median VATD). Additionally, Cox proportional hazards models were utilized to evaluate the association between VATD and OS, adjusting for age at diagnosis, sex, race/ethnicity, skeletal muscle index (SMI), skeletal muscle density (SMD), and cancer stage. Results: A total of 190 patients were included, with a median age at diagnosis of 68 years (IQR: 64-75), 56% male, 72% non-Hispanic White, and 40% diagnosed with Stage IV disease. The median SMI and SMD were 42.06 (IQR: 33.81 - 49.52) cm 2 /m 2 and 38.68 HU (IQR: 31.38 - 44.89) respectively. The median VATD was -86.14 HU (IQR: -93.78 – -76.39). Over a median follow-up of 60 months, 96 patients (51%) died. Median OS was 27 months for patients with low VAT and 62 months for those with high VAT (log-rank test, p < .001). After adjusting for confounders, VATD remained independently associated with OS (adjusted Hazard Ratio: 1.41 per IQR decrease; 95% CI: 1.06 – 1.86; p ≤ .05), indicating that each IQR decrease in VATD scores (implying an increase in VAT) is associated with a 41% increased risk of all-cause mortality. Conclusions: Our findings demonstrate that increased visceral adipose tissue, indicated by more negative VATD scores, is significantly associated with poorer survival outcomes among older adults with CRC. These results underscore the importance of dietary and weight loss interventions to improve outcomes in this population.

Morbidity and Mortality Risk Among People With Human Immunodeficiency Virus and Central or Visceral Adiposity: A Targeted Literature Review.

Given the known relationship between human immunodeficiency virus (HIV), antiretroviral therapies, and excess visceral adipose tissue (VAT), this review sought to characterize risk of negative health outcomes associated with excess VAT and increased waist circumference (WC) in people with HIV (PWH). Comprehensive targeted literature searches were conducted in Medline/Embase (27 June 2022), identifying peer-reviewed articles and conference abstracts reporting on cohorts of PWH. Screening was guided by PECOS (Population, Exposure, Comparator, Outcomes, Study design) criteria. From the included studies, outcomes of interest including mortality and morbidity risk by VAT area and WC were extracted, overall, and by sex, race/ethnicity, and duration of HIV. Relationships between outcome and exposure variables were summarized. Thirty-five studies were included (sample size range: 31-1748 PWH). Twenty-five studies characterized the relationship between increased WC and negative health outcomes-cardiovascular disease (CVD), arteriosclerosis, hypertension, diabetes, hepatic fat and fibrosis, and cognitive impairment-among PWH. Fifteen studies reported on increased VAT and negative health outcomes: all-cause mortality, CVD, atherosclerosis, hepatic fat, and fibrosis. Importantly, there was a 2.1-times higher odds of 5-year all-cause mortality among PWH with the highest amount of VAT in the only study identified reporting on mortality. Among the studies characterizing the relationship between morbidity and VAT, for example, 1 found that, for each 10-cm2 increase in VAT, the risk of prevalent CVD increased by 1.05 (95% CI: 1.0-1.1) times. WC may be a useful and cost-effective surrogate for visceral adiposity, which is an important marker of morbidity and mortality among PWH.

Association of visceral adipose tissue with echocardiographic abnormalities in type 2 diabetes patients

Abstract Introduction Ectopic deposition of adipose tissue, particularly visceral adipose tissue (VAT) has been identified as a significant contributor to cardiometabolic complications among individuals with type 2 diabetes (T2D). An increase in VAT has been suggested to cause cardiac dysfunction, which may lead to echocardiographic abnormalities such as alterations in speckle-tracking and left ventricular ejection fraction (LVEF). However, this relationship has not been fully elucidated. Purpose This study aims to determine the association between VAT and echocardiographic abnormalities in patients with T2D. Methods A cross-sectional study in a tertiary hospital which included 195 individuals with T2D, the diagnosis of autoimmune diabetes was excluded. VAT was measured using electrical bioimpedance (BIA), and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the association between VAT and echocardiographic parameters, with significance set at p < 0.05. Results Within our cohort, the median age was 57 years, with 37% men. Based on the third quartile (P75) cutoff (5 liters for men, 3.75 liters for women), the population was categorized into P1-75 and P75-100 (Table). There were significant differences in LVEF (61% in P1-75 vs. 58% in P75-100, p = 0.041), left ventricular global longitudinal strain (LV GLS) (P1-75: -20.3%, P75-100: -19.2%, p = 0.012), and conduit phase of left atrial strain (LAScd) (P1-75: 25%, P75-100: 20%, p = 0.046). Positive correlations (Figure) were observed between VAT and indexed LV mass (r = 0.171, p = 0.020), basal diameter of the right ventricle (r = 0.308, p = 0.001), and LV GLS (r = 0.197, p = 0.006). Additionally, negative correlations were observed between VAT and LVEF (r = -0.342, p = <0.001) and right ventricular fractional area change (r = - 0.227, p= 0.001). Conclusion Increased VAT was associated with cardiac dysfunction, as indicated by altered LV GLS and LAScd. This study underscores the relevance of VAT in influencing both functional and structural changes in the left and right ventricles. It also highlights the significance of monitoring VAT for comprehensive cardiovascular risk assessment in T2D patients.Clinical demographics tableScatter plots with correlation graphs

Association between asthma and visceral adipose tissue in adults, a cross-sectional study from NHANES 2011-2018.

Asthma is a chronic inflammatory disease that affects millions of people worldwide. Obesity, particularly visceral adipose tissue (VAT), is known to secrete adipokines and pro-inflammatory factors, which are closely associated with various metabolic and cardiovascular diseases. Research indicates that these metabolic disturbances can exacerbate inflammatory conditions, contributing to both cardiovascular and respiratory diseases, including asthma. Despite these associations, studies on the specific relationship between VAT and asthma remain limited and warrant further investigation. Utilizing the NHANES database from 2011 to 2018, we included a total of 11,137 participants. Multivariable regression analysis was performed, stratifying subjects based on VAT levels and adjusting for various confounders. Subgroup interaction analysis and nonlinear analysis were conducted to explore potential effect modifiers and nonlinear associations. In this study, 11,137 participants were included, with 49.74% being female. Among the 509 asthma patients, 69.35% were female. The number of asthma patients among Non-Hispanic Whites was 212, representing 41.65% of the total, the highest proportion among the studied groups. The VAT for asthma patients was 529g, significantly higher than the 455g in the non-asthma group (P < 0.001). Multivariable regression analysis showed that for every 200g increase in VAT, the risk of asthma increased by 10.4% (P = 0.032), 20.8% (P < 0.001), and 20.3% (P = 0.004) across three models (unadjusted, adjusted for demographic factors, and fully adjusted). Subgroup analysis indicated a stronger association between VAT and asthma risk in females and individuals over 40 years old. Nonlinear analysis uncovers a J-shaped relationship between VAT and asthma, with the lowest risk observed at 464.57g (P < 0.001). The study findings suggest that increased VAT is associated with elevated asthma risk, particularly among females and older individuals. These results underscore the importance of considering VAT in asthma risk assessment and highlight potential targeted interventions to reduce asthma risk associated with excess visceral adiposity.

A long-term high-fat diet induces differential gene expression changes in spatially distinct adipose tissue of male mice.

The accumulation of visceral adipose tissue (VAT) is strongly associated with cardiovascular disease and diabetes. In contrast, individuals with increased subcutaneous adipose tissue (SAT) without corresponding increases in VAT are associated with a metabolic healthy obese phenotype. These observations implicate dysfunctional VAT as a driver of disease processes, warranting investigation into obesity-induced alterations of distinct adipose depots. To determine the effects of obesity on adipose gene expression, male mice (n = 4) were fed a high-fat diet to induce obesity or a normal laboratory diet (lean controls) for 12-14 mo. Mesenteric VAT and inguinal SAT were isolated for bulk RNA sequencing. AT from lean controls served as a reference to obesity-induced changes. The long-term high-fat diet induced the expression of 169 and 814 unique genes in SAT and VAT, respectively. SAT from obese mice exhibited 308 differentially expressed genes (164 upregulated and 144 downregulated). VAT from obese mice exhibited 690 differentially expressed genes (262 genes upregulated and 428 downregulated). KEGG pathway and GO analyses revealed that metabolic pathways were upregulated in SAT versus downregulated in VAT while inflammatory signaling was upregulated in VAT. We next determined common genes that were differentially regulated between SAT and VAT in response to obesity and identified four genes that exhibited this profile: elovl6 and kcnj15 were upregulated in SAT/downregulated in VAT while trdn and hspb7 were downregulated in SAT/upregulated in VAT. We propose that these genes in particular should be further pursued to determine their roles in SAT versus VAT with respect to obesity.NEW & NOTEWORTHY A long-term high-fat diet induced the expression of more than 980 unique genes across subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The high-fat diet also induced the differential expression of nearly 1,000 AT genes. We identified four genes that were oppositely expressed in SAT versus VAT in response to the high-fat diet and propose that these genes in particular may serve as promising targets aimed at resolving VAT dysfunction in obesity.

Visceral and subcutaneous adiposity and cardiovascular disease: Unravelling associations and prognostic value.

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.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Change in abdominal obesity after colon cancer surgery – effects of left-sided and right-sided colonic resection

BackgroundExcess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots.Material and methodsComputed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately.ResultsA total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2–9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2–6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2–7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4–9%, p < 0.001) increase in SAT and a 4% (95% CI: 1–7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2–10%, p < 0.01) after 3 years.ConclusionAfter 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

Behind BMI: The Potential Indicative Role of Abdominal Ectopic Fat on Glucose Metabolism

Introduction: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. Methods: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. Results: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). Conclusion: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

Profiling of Skeletal Muscle and Adipose Tissue Depots in Men with Advanced Prostate Cancer Receiving Different Forms of Androgen Deprivation Therapy

BackgroundAndrogen deprivation therapy (ADT) is a common treatment modality for men with prostate cancer. Increases in adipose tissue mass and decreases in skeletal muscle mass are known on-target adverse effects of standard ADT. The effects of newer agents such as abiraterone acetate (ABI) and enzalutamide (ENZA) on body composition and how these compare with standard luteinizing hormone-releasing hormone agonists (aLHRHs) are unclear. ObjectiveTo assess the effects of different forms of androgen deprivation therapy on body composition in men with prostate cancer. Design, setting, and participantsUsing a retrospective design, 229 patients receiving aLHRHs alone (n = 120) or in combination with ABI (n = 53) or ENZA (n = 56) were studied. Outcome measurements and statistical analysisMuscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at baseline, 6 mo, and 18 mo after initiating therapy using a cross-sectional densitometry analysis performed on standard of care computed tomography images. Response trajectories for all treatment groups were calculated via a two-way analysis of variance post hoc test, for both within-group and between-group differences. Results and limitationsTreatment with aLHRHs, ABI, and ENZA was associated with a median muscle volume loss of –1.4%, –4.8%, and –5.5% at 6 mo, and –7.1%, –8.1%, and –8.3% at 18 mo, respectively. Therapy with aLHRHs was associated with minimal changes in VAT (0.3% at 6 mo and –0.1% at 18 mo). ABI therapy was associated with significant increases in VAT at 6 mo (4.9%) but not at 18 mo (0.5%), and ENZA therapy was associated with significant decreases in VAT (–4.6% at 6 mo and –5.4% at 18 mo). With respect to SAT, treatment with aLHRHs was associated with increases over time (8.6% at 6 mo and 4.7% at 18 mo), ABI was associated with decreases over time (–3.6% at 6 mo and –6.8% at 18 mo), and ENZA had no clear effects (1.7% at 6 mo and 3.3% at 18 mo). ConclusionsADT regimens cause significant short-term losses in muscle mass, with the most rapid effects occurring with ABI and ENZA. The three regimens have disparate effects on SAT and VAT, suggesting distinct roles of androgens in these tissues. Patient summaryAndrogen deprivation therapy alters body composition in men with prostate cancer. Abiraterone and enzalutamide are associated with losses in muscle mass compared with luteinizing hormone-releasing hormone agonists. These treatments impact subcutaneous and visceral fat mass, suggesting distinct roles of androgens in these tissues.

Impact of Liver Transplantation on Adipose Tissue Compartments and Its Association With Metabolic Sequela.

Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (β-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (β-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (β-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.

Analysis of significant weight gain in patients using alectinib for ALK-positive lung cancer.

e21138 Background: Alectinib is standard of care for metastatic anaplastic lymphoma kinase positive (ALK+) nonsmall cell lung cancer (NSCLC). Weight gain is an unexplored side effect reported in ~10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. Methods: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were quantified using sliceOmatic software on computed tomography (CT) images at baseline, three months (3M) and one year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with &gt; 10 kg weight gain were referred to Erasmus MC Obesity Center for in-depth analysis (dietary habits, metabolic/endocrine assessment). Results: Mean increase in waist circumference was 9 cm (9.7%, p &lt; 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p &lt; 0.001) in 1Y. SAT increased 18.8 cm2 (12.4%, p &lt; 0.001) in 3M and 45.4 cm2 (33.3%, p &lt; 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis showed increased appetite in two patients and metabolic syndrome in all four patients. Conclusions: Alectinib caused significant increased abdominal obesity, sarcopenic obesity, SAT and VAT quickly after initiation. This may lead to serious metabolic disturbances in long-surviving patients.[Table: see text]

0006 Circadian Misalignment Increases the Impact of Visceral Adiposity on Metabolic Syndrome Burden in Adolescents

Abstract Introduction Although insufficient sleep is a known risk factor for metabolic syndrome (MetS), the circadian timing of sleep is also involved in cardiac and metabolic regulation. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may independently impact the burden of MetS in youth. Methods We analyzed data from 277 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 5 nights of at-home actigraphy (ACT), an in-lab 9-h polysomnography (PSG) and an in-lab dual-energy X-ray absorptiometry (DEXA) scan. Two ACT-measured metrics of circadian misalignment were examined as effect modifiers: sleep midpoint (SM), the intra-individual mean midpoint of the sleep period, and sleep regularity (SR), the intra-individual standard deviation of sleep midpoint. DEXA-measured visceral adipose tissue (VAT) was the primary predictor. A continuous MetS score (i.e., sum of the age and sex adjusted z-scores of waist circumference, blood pressure, HOMA-IR, triglycerides, and HDL cholesterol) was the primary outcome. Linear regression models tested SM and SR as effect modifiers of the association of VAT with MetS, while accounting for sex, race/ethnicity, age, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results A significant interaction was found between VAT and SR on MetS (p-interaction=0.05), while not between VAT and SM (p-interaction=0.15). Among adolescents with high sleep irregularity (≥ 45 minutes; n=164), each standard deviation increase in VAT was associated with 2.4 (0.2) standard deviations increase in MetS (p&amp;lt; 0.01), while this association was weaker among adolescents with low sleep irregularity [&amp;lt; 45 minutes; n=113; β=1.7 (0.3), p&amp;lt; 0.01]. Conclusion An irregular circadian timing of sleep may further increase the impact of visceral adiposity on MetS burden in adolescents. Sleep irregularity, independent of sleep apnea and insufficient sleep, may contribute to the development of cardiometabolic sequelae associated with central obesity. Support (if any) National Institutes of Health (R01HL136587, UL1TR000127) and American Heart Association (23PRE1011962)

Analysis of Serious Weight Gain in Patients Using Alectinib for ALK-Positive Lung Cancer

IntroductionAlectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. MethodsChange in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle were quantified using sliceOmatic software on computed tomography images at baseline, 3 months (3M), and 1 year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with more than 10 kg weight gain were referred to Erasmus MC Obesity Center CGG for in-depth analysis (e.g., assessments of appetite, dietary habits, other lifestyle, medical and psychosocial factors, and extensive metabolic and endocrine assessments, including resting energy expenditure). ResultsMean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased to 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased to 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis (n = 4) revealed increased appetite in two patients and metabolic syndrome in all four patients. ConclusionsAlectinib may cause relevant increased sarcopenic abdominal obesity, with increases of both VAT and SAT, quickly after initiation. This may lead to many serious metabolic, physical, and mental disturbances in long-surviving patients.

The Longitudinal Changes in Subcutaneous Abdominal Tissue and Visceral Adipose Tissue Volumetries Are Associated with Iron Status.

Excess iron is known to trigger adipose tissue dysfunction and insulin resistance. Circulating markers of iron status have been associated with obesity and adipose tissue in cross-sectional studies. We aimed to evaluate whether iron status is linked to changes in abdominal adipose tissue longitudinally. Subcutaneous abdominal tissue (SAT) and visceral adipose tissue (VAT) and its quotient (pSAT) were assessed using magnetic resonance imaging (MRI), at baseline and after one year of follow-up, in 131 (79 in follow-up) apparently healthy subjects, with and without obesity. Insulin sensitivity (euglycemic- hyperinsulinemic clamp) and markers of iron status were also evaluated. Baseline serum hepcidin (p = 0.005 and p = 0.002) and ferritin (p = 0.02 and p = 0.01)) were associated with an increase in VAT and SAT over one year in all subjects, while serum transferrin (p = 0.01 and p = 0.03) and total iron-binding capacity (p = 0.02 and p = 0.04) were negatively associated. These associations were mainly observed in women and in subjects without obesity, and were independent of insulin sensitivity. After controlling for age and sex, serum hepcidin was significantly associated with changes in subcutaneous abdominal tissue index (iSAT) (β = 0.406, p = 0.007) and visceral adipose tissue index (iVAT) (β = 0.306, p = 0.04), while changes in insulin sensitivity (β = 0.287, p = 0.03) and fasting triglycerides (β = -0.285, p = 0.03) were associated with changes in pSAT. These data indicated that serum hepcidin are associated with longitudinal changes in SAT and VAT, independently of insulin sensitivity. This would be the first prospective study evaluating the redistribution of fat according to iron status and chronic inflammation.

Body Composition in Patients with Follicular Lymphoma: Asso-Ciations between Changes in Radiomic Parameters in Patients Treated with R-CHOP-like and R-B Regimens: LyRa 01F

In patients with follicular lymphoma (FL), therapeutic advances have led to improved survival, and within this framework, it is important to identify treatment strategies offering a better quality of life. Using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), in patients treated with R-CHOP-like or R-Bendamustine regimens, we assessed changes in the bone mineral density (BMD), musculoskeletal index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at disease onset and at the end of therapy. We evaluated whether the high-steroid regimen could lead to more significant radiological changes than those induced by the steroid-free regimen and whether a low BMD at disease onset is an unfavorable prognostic index. Seventy-nine patients between 60 and 80 years old with a new diagnosis of FL were included in the study. Evaluation of Delta values (pre- and post-therapy mean values) in the two immunochemotherapy regimens showed differences in radiomic parameters within the two patient cohorts. The R-CHOP-like regimen was associated with a significant reduction in BMD, an increase in SAT and VAT, and a reduction in skeletal muscle density (SMD) and SMI. Moreover, patients with high FLIPI showed a BMD below the cut-off value. This study represents the first study demonstrating a prognostic correlation between FLIPI and low BMD.

Accumulation in Visceral Adipose Tissue Over 6 Years Is Associated With Lower Paraspinal Muscle Density.

Visceral adipose tissue (VAT) has been recognized to be a metabolically active fat depot that may have paracrine effects on surrounding tissues, including muscle. Since many adults accumulate VAT as they age, the effect of changes in VAT on muscle is of interest. We determined the association between 6-year changes in VAT and paraspinal muscle density, an indicator of fatty infiltration. This study included 1145 participants from the Framingham Study third-generation cohort who had both quantitative computed tomography scans of the spine at baseline and 6-year's follow-up, on whom muscle density was measured along with VAT. We implemented multiple regression to determine the association of muscle density at follow-up as primary outcome measure with changes in VAT (follow-up minus baseline divided by 100), adjusting for VAT at baseline, age, sex, height, menopausal status, presence of diabetes, and physical activity. Analyses were performed in men and women separately. After adjustment for covariates, individuals with the greatest accumulation of VAT over 6 years had significantly lower paraspinal density at the follow-up with an estimated 0.302 (95% CI, -0.380 to -0.224) and 0.476 (95% CI: -0.598 to -0.354) lower muscle density (HU) per 100-cm3 increase in VAT (both P values < .001) in men and women, respectively. These results highlight that age-related accumulation of VAT in men and women is associated with lower muscle density. VAT may represent a modifiable risk factor for poor musculoskeletal outcomes with aging.

Associations Of Visceral Adipose Tissue With Chronological And BrainAge

New analytic approaches that leverage machine learning have been developed to assess biological brain age (BrainAge), as opposed to chronological age. The difference between chronological age and BrainAge (Brain Predicted Age Difference [BPAD]) may be an important health indicator, which invites exploration of factors associated with variation in BPAD. While adipose tissue in general, and visceral adipose tissue (VAT) in particular, has been associated with numerous chronic diseases and adverse outcomes in some specific brain structures, to our knowledge there has been no exploration of the relationship between VAT and BPAD. PURPOSE: To explore the associations of chronological age, BrainAge, and BPAD with VAT in older adults (65-85 yrs). METHODS: Healthy women (n = 404) and men (n = 149), mean age 72 ± 5 yrs, were assessed for VAT by Dual X-Ray Absorptiometry and received a structural MRI scan processed using the BrainAgeR algorithm developed by Cole et al (2018) using voxel-based features from a training sample of adults (n = 3377) aged 18-92, to derive BrainAge. Pearson correlation was used to assess associations between VAT and both chronological age and BrainAge, and linear regression was utilized to further assess the association between VAT and BPAD, adjusted for chronological age, sex, and physical activity. RESULTS: VAT was significantly associated with BrainAge (r(551) = 0.133 p < 0.002) but not chronological age (r(551) = 0.004 p = 0.460). VAT significantly predicted BPAD after adjusting for sex, chronological age, and physical activity (p = .001) with each unit of increase of VAT predicting a 0.99 year difference in BPAD (indicating an older than chronological age brain) as shown in Table 1.CONCLUSION: Higher VAT mass was associated with more advanced brain age as determined by the BrainAgeR technique. Future research should determine if changes in VAT deposition may positively affect brain structure in older adults.

The correlations of abdominal adipose tissue with anthropometric and metabolic parameters in obese children by magnetic resonance imaging

Objective: To explore abdominal fat mass distribution and contents among obese children via magnetic resonance imaging (MRI), and analyze the correlations of abdominal adipose tissue with anthropometric and metabolic parameters. Methods: Cross-sectional study. There were 60 obese children admitted to the Children's Health Care Department and Endocrinology Department at Children's Hospital of Nanjing Medical University from July 2016 to December 2018. Children's gender, age, height, weight, body composition, waist circumference and blood pressure were recorded. The levels of fasting blood glucose, lipids, insulin were measured, and liver ultrasound was performed, and the body mass index Z score (BMI-Z), waist-to-height ratio (WHtR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. In addition, contents of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) were calculated according to feedback of abdominal MRI scan images. The associations between the contents of abdominal adipose tissue, physical examination status and metabolic disorders among obese children were analyzed through correlation analysis and regression analysis. Receiver operating characteristic (ROC) curve was used to compare the accuracy of fat mass in different parts of the abdomen in predicting their metabolic disorders. Results: A total of 60 children were enrolled in the study, included 44 boys and 16 girls, with age of (9.2±1.4) years. The contents of SAT, VAT and TAAT among the 60 children were positively associated with BMI-Z (r=0.60, 0.46, 0.59), body fat percentage (r=0.64, 0.67, 0.68) and waist-to-height ratio (r=0.60, 0.57, 0.61) (all P<0.01). Meanwhile, contents of SAT and TAAT were also positively correlated with systolic blood pressure (r=0.47, 0.49), triglyceride (r=0.33, 0.35) and HOMA-IR (r=0.33, 0.28)(all P<0.05). In order to adjust the confounding effects among various variables, regression analysis was applied and the result showed that the body fat percentage (β=0.59, 0.66, 0.65) and waist-to-height ratio (β=0.53, 0.63, 0.59) were most related to abdominal fat contents (all P<0.01), including SAT, VAT and TAAT among obese children. According to ROC, SAT had outstanding evaluation performances for the diagnosis of insulin resistance and metabolic syndrome, while VAT had excellent evaluation performances for non-alcoholic fatty liver disease (area under curve=0.68, 0.69, 0.69, 95%CI 0.54-0.82, 0.55-0.84, 0.53-0.85, P=0.017, 0.014, 0.019). Conclusions: As one of the best indexes, body fat percentage and WHtR can be used to predict the contents of SAT, VAT and TAAT among obese children. With the increase of abdominal SAT or VAT, the risks for insulin resistance, metabolic syndrome and non-alcoholic fatty liver disease would increase. Assessment of abdominal fat and metabolic risks in obese children should combine BMI-Z with waist circumference and body composition analysis.