Changes In Visceral Adipose Tissue Research Articles

Early-Life Risk Factors for Carotid Intima-Media Thickness and Carotid Stiffness in Adolescence

ImportanceAtherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life.ObjectiveTo identify early-life risk factors for preclinical atherosclerosis in adolescence.Design, Setting, and ParticipantsThis cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands. Eligible participants included those from the WHISTLER cohort who visited the clinic between March 2019 and October 2020 for adolescent follow-up. This study’s analyses were performed in January 2024.ExposuresEarly-life growth was assessed at birth to 6 months, 5 years, and 12 to 16 years. Abdominal ultrasonography determined abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depth. Blood pressure (BP) percentiles and body mass index (BMI) z scores were used.Main Outcomes and MeasuresCarotid ultrasonography was performed at age 12 to 16 years to assess carotid intima-media thickness (cIMT) and the distensibility coefficient (DC), established measures of preclinical atherosclerosis. Multivariable linear regression models were used to identify early-life risk factors for cIMT and DC in adolescence.ResultsIn total, 232 adolescents (median [IQR] age, 14.9 [13.7-15.8] years; 121 female [52.2%]) were included. More postnatal weight gain (B = 12.34; 95% CI, 2.39 to 22.39), higher systolic BP at 5 years (B = 0.52; 95% CI, 0.02 to 1.01), more VAT at 5 years (B = 3.48; 95% CI, 1.55 to 5.40), and a larger change in VAT between 5 and 12 to 16 years (B = 3.13; 95% CI, 1.87 to 4.39) were associated with a higher cIMT in adolescence. A higher BMI (B = −2.70, 95% CI,−4.59 to −0.80) and VAT at 5 years (B = −0.56; 95% CI, −0.87 to −0.25), as well as a larger change in BMI between 5 and 12 to 16 years (B = −3.63; 95% CI, −5.66 to −1.60) were associated with a higher carotid stiffness in adolescence. On the contrary, a larger change in SAT between 5 and 12 to 16 years (B = 0.37; 95% CI, 0.16 to 0.58) was associated with a higher carotid DC in adolescence.Conclusions and RelevanceIn this cohort study of 232 participants, early-life growth parameters, and particularly abdominal VAT development, were associated with a higher cIMT and carotid stiffness in adolescence. These findings suggest that assessment of adipose tissue development during childhood can aid characterization of lifetime risk trajectories and tailoring of cardiovascular prevention and risk management strategies.

Impact of diet intervention on visceral adipose tissue and hepatic fat in patients with obesity or type 2 diabetes: a randomized trial

This study aimed to assess the effects of a diet intervention on visceral and hepatic fat in patients with obesity or type 2 diabetes (T2D). Participants with obesity or T2D were randomized to a diet intervention or their usual diet. The intervention comprised a “3G rice” regimen combined with a low-salt, high-fiber diet. The primary outcomes were changes in visceral adipose tissue (VAT) area and hepatic fat over 12 weeks assessed by magnetic resonance imaging. Eighty-six patients were randomized. Their mean age was 47.5 ± 11.0 years, and 82.3% were female. Eighty-one (94.2%) had obesity, and 16 (18.6%) had T2D. Baseline metrics were body weight 76.3 ± 16.1 kg, BMI 29.6 ± 4.6, VAT 12 629 ± 5819 mm2, and hepatic fat 7.9% ± 7.2%. At the 12-week follow-up, the diet group had greater VAT and hepatic fat reductions than controls (− 1468 ± 1468 vs. − 179 ± 1576 mm2, P = 0.001; and − 2.6% ± 3.4% vs. 0.4% ± 2.2%, P < 0.001). Adjusted differences remained significant for VAT (− 1093 mm2, P < 0.001) and hepatic fat (− 2.5%, P < 0.001). In conclusion, the 12-week diet intervention decreased VAT, hepatic fat, body weight, and BMI compared to a usual diet.

Diabetes-specific formula with standard of care improves glycemic control, body composition, and cardiometabolic risk factors in overweight and obese adults with type 2 diabetes: results from a randomized controlled trial.

Medical nutrition therapy is important for diabetes management. This randomized controlled trial investigated the effects of a diabetes-specific formula (DSF) on glycemic control and cardiometabolic risk factors in adults with type 2 diabetes (T2D). Participants (n = 235) were randomized to either DSF with standard of care (SOC) (DSF group; n = 117) or SOC only (control group; n = 118). The DSF group consumed one or two DSF servings daily as meal replacement or partial meal replacement. The assessments were done at baseline, on day 45, and on day 90. There were significant reductions in glycated hemoglobin (-0.44% vs. -0.26%, p = 0.015, at day 45; -0.50% vs. -0.21%, p = 0.002, at day 90) and fasting blood glucose (-0.14 mmol/L vs. +0.32 mmol/L, p = 0.036, at day 90), as well as twofold greater weight loss (-1.30 kg vs. -0.61 kg, p < 0.001, at day 45; -1.74 kg vs. -0.76 kg, p < 0.001, at day 90) in the DSF group compared with the control group. The decrease in percent body fat and increase in percent fat-free mass at day 90 in the DSF group were almost twice that of the control group (1.44% vs. 0.79%, p = 0.047). In addition, the percent change in visceral adipose tissue at day 90 in the DSF group was several-fold lower than in the control group (-6.52% vs. -0.95%, p < 0.001). The DSF group also showed smaller waist and hip circumferences, and lower diastolic blood pressure than the control group (all overall p ≤ 0.045). DSF with SOC yielded significantly greater improvements than only SOC in glycemic control, body composition, and cardiometabolic risk factors in adults with T2D.

Improvement in Visceral Adipose Tissue and LDL Cholesterol by High PUFA Intake: 1-Year Results of the NutriAct Trial.

We assessed the effect of a dietary pattern rich in unsaturated fatty acids (UFA), protein and fibers, without emphasizing energy restriction, on visceral adipose tissue (VAT) and cardiometabolic risk profile. Within the 36-months randomized controlled NutriAct trial, we randomly assigned 502 participants (50-80 years) to an intervention or control group (IG, CG). The dietary pattern of the IG includes high intake of mono-/polyunsaturated fatty acids (MUFA/PUFA 15-20% E/10-15% E), predominantly plant protein (15-25% E) and fiber (≥30 g/day). The CG followed usual care with intake of 30% E fat, 55% E carbohydrates and 15% E protein. Here, we analyzed VAT in a subgroup of 300 participants via MRI at baseline and after 12 months, and performed further metabolic phenotyping. A small but comparable BMI reduction was seen in both groups (mean difference IG vs. CG: -0.216 kg/m2 [-0.477; 0.045], partial η2 = 0.009, p = 0.105). VAT significantly decreased in the IG but remained unchanged in the CG (mean difference IG vs. CG: -0.162 L [-0.314; -0.011], partial η2 = 0.015, p = 0.036). Change in VAT was mediated by an increase in PUFA intake (ß = -0.03, p = 0.005) and induced a decline in LDL cholesterol (ß = 0.11, p = 0.038). The NutriAct dietary pattern, particularly due to high PUFA content, effectively reduces VAT and cardiometabolic risk markers, independent of body weight loss.

Abstract P346: Effect of Low-Fat versus Low-Carbohydrate Diet on Visceral Fat

Introduction: A healthy low fat (HLF) and healthy low carbohydrate (HLC) diet are common strategies for weight loss that vary in their effects on adiposity and metabolism. Visceral adipose tissue (VAT) is the major contributor to metabolism deregulation, beyond subcutaneous adipose tissue (SAT). Despite strong biological evidence that a HLC diet preferentially decreases VAT relative to SAT, the difficulty in measuring adipose sub-types has impeded its use in diet trials. To address this research gap, we measured VAT and SAT in a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) weight loss trial to compare the effects of HLF and HLC diets and potential effect modification by sex and insulin resistance status. Hypothesis: We hypothesized that a HLC diet is associated with greater VAT loss compared with a HLF diet. Secondly, we hypothesized that men and those with greater baseline insulin secretion assigned to HLC diet would experience greater VAT loss. Methods: DIETFITS was a single-site, parallel-group, weight loss diet trial, randomizing 609 adults with overweight and obesity to a HLC or HLF diet for 12 months. Data collection occurred at baseline, 6 months, and 12 months. Insulin resistance status was proxy measured using insulin concentration 30 minutes after a glucose challenge (INS 30). In this secondary analysis, we measured VAT and SAT in the abdominal region by reanalyzing the dual-energy x-ray absorptiometry (DXA) scans. We fit a linear mixed model to evaluate the change in VAT after 6 and 12 months on HLF and HLC, with fixed effects: time, diet, and their interaction; and a random effect for repeated observations. We built separate models for each of the secondary hypotheses, with additional fixed effects INS 30 and sex, respectively. Results: We included 449 participants with baseline DXA (60% women; mean age 40 years). From baseline to 6-months, participants assigned to a HLC diet experienced a significant 10.6 cm 2 (95% CI: 5.1, 16.1) greater decrease in mean VAT compared to those assigned to a HLF diet. The 12-month difference in diets attenuated to 5.5 cm 2 (95% CI: -0.1, 11.1). Contrary to our hypothesis, INS 30 did not modify the diet-related changes in VAT. Among men, both diets resulted in a 12-month decrease in VAT. The HLC diet was associated with a 12.1 cm 2 (95% CI: 1.6, 22.7) greater loss of VAT compared to HLF. Among women, HLF but not HLC was associated with decreased VAT, and there was no difference in VAT loss between diets 1.8 cm 2 (95% CI: -4.1, 7.6). Models controlling for SAT indicated that VAT decreased independently of SAT. Conclusion: These findings contribute to the understanding of the nuanced impacts of HLF and HLC diets on adipose sub-types and underscore the relevance of considering sex in designing effective dietary interventions targeting VAT reduction and metabolic health.

The effect of bariatric surgery type on cardiac reverse remodelling.

Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.

Inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A2AR improves hepatic and cardiac dysfunction of NASH mice.

A2AR-disrupted mice is characterized by severe systemic and visceral adipose tissue (VAT) inflammation. Increasing adenosine cyclase (AC), cAMP, and protein kinase A (PKA) formation through A2AR activation suppress systemic/VAT inflammation in obese mice. This study explores the effects of 4 wk A2AR agonist PSB0777 treatment on the VAT-driven pathogenic signals in hepatic and cardiac dysfunction of nonalcoholic steatohepatitis (NASH) obese mice. Among NASH mice with cardiac dysfunction, simultaneous decrease in the A2AR, AC, cAMP, and PKA levels were observed in VAT, liver, and heart. PSB0777 treatment significantly restores AC, cAMP, PKA, and hormone-sensitive lipase (HSL) levels, decreased SREBP-1/FASN, MCP-1, and CD68 levels, reduces infiltrated CD11b+ F4/80+ cells and adipogenesis in VAT of NASH + PSB0777 mice. The changes in VAT were accompanied by the suppression of hepatic and cardiac lipogenic/inflammatory/injury/apoptotic/fibrotic markers, the normalization of cardiac contractile [sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2)] marker, and cardiac dysfunction. The in vitro approach revealed that conditioned media (CM) of VAT of NASH mice (CMnash) trigger palmitic acid (PA)-like lipotoxic (lipogenic/inflammatory/apoptotic/fibrotic) effects in AML-12 and H9c2 cell systems. Significantly, A2AR agonist pretreatment-related normalization of A2AR-AC-cAMP-PKA levels was associated with the attenuation of CMnash-related upregulation of lipotoxic markers and the normalization of lipolytic (AML-12 cells) or contractile (H9C2 cells) marker/contraction. The in vivo and in vitro experiments revealed that A2AR agonists are potential agent to inhibit the effects of VAT inflammation-driven pathogenic signals on the hepatic and cardiac lipogenesis, inflammation, injury, apoptosis, fibrosis, hypocontractility, and subsequently improve hepatic and cardiac dysfunction in NASH mice.NEW & NOTEWORTHY Protective role of adenosine A2AR receptor (A2AR) and AC-cAMP-PKA signaling against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) possibly via its actions on adipocytes is well known in the past decade. Thus, this study evaluates pharmacological activities of A2AR agonist PSB0777, which has already demonstrated to treat NASH. In this study, the inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A2AR with A2AR agonist PSB0777 improves the hepatic and cardiac dysfunction of high-fat diet (HFD)-induced NASH mice.

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.

The effect of thiazolidinediones on body fat redistribution in adults: A systematic review and meta-analysis of randomized controlled trials.

Visceral adiposity is a strong predictor of cardiometabolic risk. Thiazolidinediones (TZDs) are associated with a shift in fat redistribution from visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT). We aimed to compare the effects of TZD and other interventions on fat remodeling in adults in randomized controlled trials. Among the 1331 retrieved studies, 39 trials with 1765 participants were included in the meta-analysis. The standardized mean difference in VAT change was not significantly different between TZD and comparators across the overall studies. Intriguingly, TZD treatment resulted in significant decreases in VAT compared with placebo and sulfonylureas (p < 0.05), although recombinant human growth hormone was superior to TZD regarding VAT reduction (p < 0.05). Data from 216 participants showed TZD leading to a greater reduction in liver fat percentage than comparators (p < 0.05). Compared with the controls, TZD significantly increased SAT, total body fat, weight, waist circumference, and body mass index (p < 0.05). However, TZD pronouncedly improved glucose control, insulin resistance, adiponectin, and lipid profile (p < 0.05). TZD provides a favorable effect on fat redistribution and benefits insulin sensitivity, suggesting a potentially valuable approach in cardiometabolic risk management.

Abstract B101: Obesity mediates altered triple-negative breast cancer tumor biology in African American women independent of ancestry

Abstract African American (AA) breast cancer (BC) is associated with a higher incidence of aggressive BC phenotypes at younger age, higher grade of tumor as compared to BCs of age-matched patients of European American (EA). For AA women, there is a higher frequency of the more aggressive TNBC subtype and of the PAM50-molecular basal subtype. AA tumors are enriched for inflammatory and immune pathways, implicating inherited susceptibility associated with African ancestry. Obesity induces a state of low-grade inflammation. AA women tend to be more obese than EA and have elevated a inflammatory markers, including CRP, IL6, and IL1. Since inflammation related to obesity is a reflection of dysfunctional adipocyte biology, we used dataset GSE88837 to perform in silico analysis of gene expression changes in visceral adipose tissue for AAs and EAs. AA adipose tissue is more inflamed than EAs at the same level of obesity (BMI&amp;gt;30). There was a high expression of secreted mediators causing systemic inflammation, including heat shock protein 60 (HSPD1), CXCL1, S100A9, and SPP1. VEGFA, S100A9, and SPP, tumor-promoting angiogenic mediators, were higher in obese AAs than EAs. These data indicate that obesity enhances inflammation in visceral adipose tissue of AAs. We performed in silico analysis of dataset GSE78958, of 400 BC patients annotated for race, BMI, and hormone receptor expression. We analyzed BC patients for differential gene expression, PAM50 subtype, tumor stage and grade, based on race and BMI. AA women have a higher BMI (48.9%) than EA women (32.3%) and a higher percentage of poorly differentiated tumors (51.1%) than EAs (40.6%). AA women with BMI &amp;gt;30, had more basal-like tumors (34.8%) than EA women (19.3%). These analyses confirm that excess adiposity promotes the basal BC phenotype. With BMI &amp;gt;30 as a criterion for obesity, the GSE78958 dataset containing BCs for 96 AA and 200 EA patients was analyzed for differences in gene expression. DEGs showed upregulation of T cell exhaustion marker PTPN22 and LAIR2. The metastasis and proliferation promoting chemokines CXCL1, CCL2, CXC12, CXCR4, and S100A9 were higher in the BCs of obese AAs, than BCs of non-obese AAs. Stemness related genes, STAT1, SOX4, and KLF4, were higher in BCs of obese AAs. CD163-expressing M2 macrophages were higher in BCs of obese AAs. Our group showed that there was a considerable overlap of genes among African and AA cases, but there were some non-overlapping genes indicating that ancestry alone cannot explain the genetic diversity in the tumor phenotype of AA patients. The divergence was largely driven by an upregulated gene signature found among AAs and not seen among African patients. GSE78958 (obesity BC dataset) was mapped for ancestral correlation of altered genes in the AA BC dataset. Ancestry mapping showed an inverse correlation of HSPD1 with ancestry. Obesity upregulated HSPD1 in BCs of AAs as well as in AA adipose tissue and decreased the probability of survival for women of AA ethnicity, suggesting delineation of ancestry-specific and race-specific effects. Citation Format: Deepa Bedi, Rachel Martini, Melissa B. Davis, Clayton Yates. Obesity mediates altered triple-negative breast cancer tumor biology in African American women independent of ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B101.

The effect of bariatric surgery type on cardiac reverse remodelling

Abstract Introduction Bariatric surgery has been shown to improve adverse cardiac remodelling associated with obesity. Three operations are commonly performed: Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB). Whilst all three of these procedures result in weight loss, it is currently unclear as to which procedure is most effective at reversing cardiac remodelling. Purpose We assessed differences in cardiac remodelling following each type of surgery using cardiac magnetic resonance (CMR) imaging. Methods 58 patients underwent bariatric surgery (26 RYGB, 22 LSG and 10 LAGB) with CMR before and after surgery, including 46 with short-term (median 251, 219 and 273 days) and 43 with long-term (median 1026, 983 and 1027 days) follow-up. CMR was used to assess cardiac volumes, LV mass (LVM) and LV mass:volume ratio (LVMVR – a marker of concentric remodelling). Adipose tissue depots were also assessed during the scan, including visceral adipose tissue (VAT) at L5 level and epicardial adipose tissue (EAT) (manual contouring in end-ventricular systole on short axis slices from the mitral valve to the apex). Results Changes in percentage body weight were similar between surgery groups in the short term, but appeared to diverge in the longer term (LSG vs LAGB, p=0.039; RYGB vs LAGB, p=0.341) (Figure 1A). Percentage change in VAT and EAT however where significantly greater following RYGB and LSG compared to LAGB at both short- and long-term time points (Figure 1B). Changes in left ventricular end diastolic volume (LVEDV) were similar between groups in both the short term and long term (Figure 2A). We observed a significant difference in LVM change following RYGB or LSG versus LAGB (Figure 2B). This change in LVM at the long-term time point correlated with change in VAT normalised to body weight (r=0.3399, p=0.0368, Figure 2C). Finally, there was a significant decrease in LVMVR at the long-term time point following both RYGB (p=0.006) and LSG (p=0.021), whereas no such change was observed following LAGB (p=0.912). Conclusions Our results suggest that RYGB and LSG are significantly better at decreasing body adipose depots than LAGB. This greater reduction in visceral adipose tissue may account for the greater cardiac reverse remodelling seen with RYGB and LSG compared to LAGB.Figure 1Figure 2

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 &amp;gt; 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.

Higher visceral adipose tissue is associated with decreased memory suppression ability on food-related thoughts: A 1-year prospective ERP study

Memory about food and eating is crucial in regulating appetite and eating behaviors. Successfully stopping vivid imagination of delicious food could help reduce food craving and thus reduce the possibility of further intake. Memory inhibition is a cognitive process that involves intentional suppression of certain memories coming to consciousness. Successful memory suppression derives from inhibitory control. Although considerable work has consistently observed the impairment in motor or response inhibitory control among individuals with obesity, there has been a lack of investigation into the influence of bodyweight status on memory inhibitory control. To fill this gap, current study investigated behavioral and neurophysiological correlates of memory suppression in young women. Using Think/No-Think task and event-related potentials among 47 females, we found that participants with higher visceral adipose tissue (VAT) showed a tendency towards decreased suppression ability for memories related to food but not memories related to nonfood items. In depth analysis showed that decrease in the differences in P2 amplitudes between suppression vs. retrieval of food-related memories mediated the impairment of suppression ability by high VAT. We then tested whether individual differences in memory suppression ability as well as ERP correlates predicted future BMI or VAT change over 1-year follow-up. Results showed that P2 amplitudes when retrieving food-related memory could predict VAT change at 1-year follow-up among participants with healthy BMI. These observations suggest a hypersensitivity inference hypothesis underlying memory control impairments. To be specific, deficits in memory suppression may be in part resulted from elevated sensitivity to the cues coupling with food-related memory. It extends previous studies of memory suppression with food rewards and provides the first evidence to help understand the relationship between inhibitory control on food-related memory and obesity.

The evaluation of subcutaneous and visceral adipose tissue changes by computed tomography in coronavirus disease 2019 and comparison with quantitative analysis of lung involvement.

This study aims to reveal the relationship between lung involvement and visceral adipose tissue changes between chest-computed tomography (CT) scans taken in short intervals in COVID-19 patients. The retrospective study included 52 patients who tested positive for SARS-CoV-2. All patients had two chest CT exams. Lung involvement measurements were calculated by using an artificial intelligence tool. Visceral and subcutaneous fat tissue was measured at the level of the first lumbar vertebra on chest CT. Additionally, demographic and laboratory data were collected. 52 patients were included (36.5 % female, mean age 50). Visceral fat area and visceral fat thickness changes were significantly positive predictors of total lung involvement changes (p=0.033, p=0.00024). Subcutaneous fat area and subcutaneous fat thickness changes were not associated with lung involvement change (p>0.05). CRP, IL-6, d-dimer, and ferritin levels were higher in patients who need intensive care units. Visceral adipose tissue changes may indicate that it can have a role as a reservoir of virus involvement.

Changes in adipose tissue distribution and relation to cardiometabolic risk factors after Roux-en-Y gastric bypass in adolescents.

Roux-en-Y gastric bypass (RYGB) among adolescents with obesity results in significant weight loss; however, depot-specific changes have been understudied. We hypothesized that visceral adipose tissue (VAT) reduction in adolescents undergoing RYGB would be greater than other depots and associated with improvement in cardiometabolic risk factors. Three specialized treatment centers in Sweden. Fifty-nine adolescents underwent dual x-ray absorptiometry before surgery and at 1, 2, and 5 years after RYGB. Changes in body composition in multiple depots (total fat, lean body, gynoid fat, android fat, subcutaneous adipose tissue, and VAT) and cardiometabolic risk factors were assessed using multiple linear regression analysis and generalized estimating equations adjusting for age, sex, and baseline risk factor levels. Data are presented as percent change (95% CI) with regression models showing slopes and estimated P values. At 1 year post-RYGB, a significant reduction was observed across all body composition measures (P < .001) with the greatest reduction observed in VAT (-65.1% [-68.7, -61.8]). From year 1 to 5 years post-RYGB, a regain was observed in all depots except lean body mass (1.2% [.3, 2.7], P = .105). A sex-specific difference in overall trajectories was only observed in lean body mass with males consistently having higher mean levels. Change in VAT at 1 year correlated with change in triglycerides (slope: .21 mg/dL/kg, P = .034) and fasting plasma insulin (slope: 44 pmol/L/kg, P = .027). Adiposity measures all decreased after RYGB but poorly predicted change in cardiometabolic risk. Despite significant reductions at 1 year, a steady regain was observed out to 5 years, with values still well below baseline. Further research should consider control group comparison and extended follow-up.

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.

Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol

Background and aimsTo investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. Methods and resultsAnticipated 208 adults (50% women) aged 30–60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. ConclusionThis study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Effects of Hydroxycitric Acid Supplementation on Body Composition, Obesity Indices, Appetite, Leptin, and Adiponectin of Women with NAFLD on a Calorie-Restricted Diet.

This trial assessed the effects of a calorie-restricted diet (CRD) with hydroxycitric acid (HCA) supplementation on appetite-regulating hormones, obesity indices, body composition, and appetite in women with nonalcoholic fatty liver disease (NAFLD). This study was carried out on 44 overweight/obese women with NAFLD. The patients were randomly assigned into two groups, namely, "Intervention group" (receiving individual CRD plus HCA tablets per day) and "Control group" (receiving only CRD) for eight weeks. Obesity indices, body composition, appetite status, and serum levels of leptin and adiponectin were assessed before and after the intervention. Forty patients completed the trial. At the end of the trial, although significant reductions were found in most of the studied obesity indices in the intervention group, there was only a significant decrease in waist circumference and waist-to-height ratio in the control group. Fat mass and muscle mass significantly decreased in the intervention group (p=0.044 and p=0.024, respectively), and the reduction in visceral fat in the intervention group was significantly greater than that in the control group (-0.49 kg vs -0.37 kg, p=0.024). Intra- and intergroup differences in serum leptin and adiponectin levels and their ratios before and after the trial were not significant. We found a negative and marginally significant correlation between percent of changes in serum adiponectin level and percent of changes in visceral adipose tissue (VAT) (r = -0.429, p=0.067) and BMI (r = -0.440, p=0.059) as well as an inverse relationship between percent of changes in leptin/adiponectin with VAT (r = -0.724, p < 0.001) in the intervention group. HCA plus weight loss diet could significantly reduce visceral adipose tissue without any significant changes in serum leptin and adiponectin levels.

Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity

Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesity-metabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (inter-tissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric population.

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.