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.

Major depression recurrence is associated with differences in obesity-related traits in women, but not in men.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link. Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms. 790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants. The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Interleukin-15 and high-intensity exercise: relationship with inflammation, body composition and fitness in cancer survivors.

Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth. These anti-oncogenic effects of exercise were associated with the exercise-mediated release of myokines such as interleukin (IL)-15. However, no study has quantified the acute IL-15 response in human cancer survivors, and whether physiological adaptations to exercise training (i.e. body composition and cardiorespiratory fitness) influence this response. In the present study breast, prostate and colorectal cancer survivors (n=14) completed a single bout of high-intensity interval exercise (HIIE) [4×4min at 85-95% heart rate (HR) peak, 3min at 50-70% HR peak] before and after 7months of three times weekly high-intensity interval training (HIIT) on a cycle ergometer. At each time point venous blood was sampled before and immediately after HIIE to assess the acute myokine (IL-15, IL-6, IL-10, IL-1ra) responses. Markers of inflammation, cardiorespiratory fitness and measures of body composition were obtained at baseline and 7months. An acute bout of HIIE resulted in a significant increase in IL-15 concentrations (pre-intervention: 113%; P=0.013, post-intervention: 102%; P=0.005). Post-exercise IL-15 concentrations were associated with all other post-exercise myokine concentrations, lean mass (P=0.031), visceral adipose tissue (P=0.039) and absolute peak (P=0.032). There was no significant effect of 7months of HIIT on pre- or post-HIIE IL-15 concentrations (P>0.05). This study demonstrates HIIE is a sufficient stimulus to increase circulating IL-15 and other myokines including IL-6, IL-10 and IL-1ra which may be clinically relevant in the anti-oncogenic effect of exercise and repetitive exposure to these effects may contribute to the positive relationship between exercise and cancer recurrence. KEY POINTS: Exercise has been demonstrated to reduce the risk of cancer recurrence. Pre-clinical murine and in vitro models have demonstrated that exercise suppresses tumour and cancer cell growth, mediated by exercise-induced myokines (IL-6 and IL-15). High-intensity interval exercise significantly increased myokines associated with the anti-oncogenic effect of exercise and the magnitude of response was associated with lean mass, but training did not appear to influence this response. Given IL-15 has been implicated in the anti-oncogenic effect of exercise and is being explored as an immunotherapy agent, high-intensity interval exercise may improve outcomes for people living beyond cancer through IL-15-mediated pathways. Interventions that increase lean mass may also enhance this response.

Influence of chronic wartime stress on the course of non-alcoholic fatty liver disease

Objective — to analyze levels of chronic stress hormones in patients with non‑alcoholic fatty liver disease (NAFLD), who were exposed to psychogenic factors of wartime. Materials and methods. Examinations involved 88 patients with NAFLD, form them 38 subject were examined in the pre‑war period (comparison group), 50 patients were under the influence of stress during hostilities (main group). Control group consisted of 20 practically healthy subjects. Patients’ groups matched by age. The main group consisted of 28 men and 22 women, the comparison included 17 men and 21 women. The mean age in the main group was (51.6±7.7) years and in the comparison group (51.8±8.1) року. The trophological status of patients was monitored with the use of Body Composition Monitor.Omron BF­­511; hormones of chronic stress were assessed with solid‑phase enzyme immunoassay. Results. The assessment of levels of the chronic stress biochemical markers in NAFLD patients during the war demonstrated pronounced hyperprolactinemia in comparison with both control group and NAFLD patients examined in the pre‑war period. The dependence of stress hormone levels on the trophic status of patients and gender was revealed. A direct correlation between the prolactin level and the index of insulin resistance (IR), the percentage of visceral adipose tissue (VAT), and the level of triglycerides (TG) was revealed. A weak positive correlation was also observed between the level of brain‑derived neurotrophic factor (BDNF) and IR, VAT, TG, and C‑reactive protein (CRP). The activity of the inflammatory process depended on the level of dihydroepiandrosterone (DHEA), which confirms the direct correlation between the level of this hormone and ALT and CRP. Conclusions. The dependence of stress hormones levels on the trophic status of patients and gender was revealed. The level of DHEA in NAFLD patients with obesity and overweight significantly exceeded the corresponding indicators in the group with normal body mass index (BMI). In the group of overweight women who experienced negative consequences of military actions, the DHEA level significantly exceeded the corresponding indicators in comparison with the pre‑war period. Under the influence of military actions in patients of the main group, the reaction to stress was accompanied by an increase in prolactin levels in men with normal and overweight weight compared to the pre‑war period. In obese women from the main group, the hyperprolactinemia level significantly exceeded the corresponding values in the groups with normal and excessive BMI. The revealed correlation dependence between the stress hormones levels and metabolic factors indicates the influence of chronic stress on the main pathogenetic mechanisms of the development and progression of NAFLD in the conditions of war.

Correlation of HbA1c levels with CT-based body composition biomarkers in diabetes mellitus and metabolic syndrome

Diabetes mellitus and metabolic syndrome are closely linked with visceral body composition, but clinical assessment is limited to external measurements and laboratory values including hemoglobin A1c (HbA1c). Modern deep learning and AI algorithms allow automated extraction of biomarkers for organ size, density, and body composition from routine computed tomography (CT) exams. Comparing visceral CT biomarkers across groups with differing glycemic control revealed significant, progressive CT biomarker changes with increasing HbA1c. For example, in the unenhanced female cohort, mean changes between normal and poorly-controlled diabetes showed: 53% increase in visceral adipose tissue area, 22% increase in kidney volume, 24% increase in liver volume, 6% decrease in liver density (hepatic steatosis), 16% increase in skeletal muscle area, and 21% decrease in skeletal muscle density (myosteatosis) (all p < 0.001). The multisystem changes of metabolic syndrome can be objectively and retrospectively measured using automated CT biomarkers, with implications for diabetes, metabolic syndrome, and GLP-1 agonists.

Association between endogenous sex hormones and adiposity in youth across a weight status spectrum.

While endogenous sex hormones (e.g., testosterone, estradiol) are important factors regulating adipose tissue distribution, studies evaluating such relationships in youth across a wide weight status spectrum are limited. We performed a cross-sectional analysis of 8-21-year-old youth. Multiple linear regression models were used to evaluate associations between sex hormones and adiposity measures (android/gynoid ratio (A/G), total fat mass (FM), visceral adipose tissue (VAT), waist circumference (WC)) and total lean mass (LM), adjusting for pubertal stage and race/ethnicity, and stratified by sex and weight status. Among 342 youth, the mean age was 13.0 ± 2.8 years old (52.6% female; 38.9% normal weight [NW]; 27.8% overweight/obesity [OW/OB]; 33.3% severe obesity [SO]). Testosterone was positively associated with LM among males with NW (1462 g, 95% CI: 255-2668 g) and OW/OB (3792 g, 95% CI: 1244-6340 g), with A/G and WC among males with NW (0.01, 95% CI: 0-0.2 and 10 mm, 95% CI: 4-16 mm, respectively), and negatively associated with WC among males with SO (-43 mm, -81 to -5 mm). Estradiol was positively associated with A/G, FM, and WC among males with SO, and VAT in females with NW. Our findings showed that sex hormones were associated with adipose tissue deposition in youth across the weight spectrum. Sex hormones (e.g., testosterone, estradiol) are associated with various adiposity measures among male and female children and adolescents across a weight status spectrum. We evaluated associations between sex hormones and various adiposity measures among 8-21-year-olds across a weight status spectrum (normal weight, overweight/class 1 obesity, class 2-3 obesity). We found that estradiol was positively associated with total fat mass, android/gynoid ratio, and waist circumference in males with class 2-3 obesity, and testosterone was positively associated with lean mass in males with normal weight and overweight/class 1 obesity. Sex hormones may influence, or may be influenced by, adiposity in youth.

Comparable glucagon-stimulated amino acid suppression in individuals with and without hepatic steatosis or steatohepatitis.

Hepatic amino acid (AA) metabolism and glucagon secretion are linked in a feedback cycle in which circulating AAs stimulate glucagon secretion, while glucagon stimulates hepatic AA catabolism. It has been proposed that metabolic dysfunction-associated steatotic liver disease (MASLD) leads to hepatic glucagon resistance, which may result in hyperaminoacidemia and hyperglucagonemia. We tested the glucagon effect on AA metabolism in subjects with obesity; 11 with steatohepatitis (MASH), 10 with steatosis (MAS), and seven subjects (CON) without steatosis. We performed a somatostatin clamp with infusions of insulin and low-dose followed by high-dose glucagon. We measured plasma levels of 17 AAs and assessed hepatic fat content (FF%) and body fat distribution (visceral and subcutaneous adipose tissue mass) by MRI. HighGlucagon suppressed plasma total AA equally in all groups; MASH 13% (SD 9%), MAS 14% (7%), CON 11% (5%), respectively. In univariate regression analyses visceral adipose tissue mass (β = 0.471, P = 0.011) and AA concentration at LowGlucagon (β = ─0.524, P = 0.004), but not FF% (β = ─0.243, P = 0.213), were significant predictors of AA reduction. Using a stepwise backward multiple regression approach revealed similar results. Total and specific AA levels (glutamic acid, tyrosine) were higher in both MASLD groups during the study and FF% was positively correlated to a number of individual AAs. Though finding elevated AA concentrations in subjects with MASLD, we conclude that in MASLD patients that do not have elevated glucagon at baseline, glucagon suppresses circulating AA levels equally in subjects with and without MASLD. NCT04042142.

Predicting post-lung transplant survival in systemic sclerosis using CT-derived features from preoperative chest CT scans.

The current understanding of survival prediction of lung transplant (LTx) patients with systemic sclerosis (SSc) is limited. This study aims to identify novel image features from preoperative chest CT scans associated with post-LTx survival in SSc patients and integrate them into comprehensive prediction models. We conducted a retrospective study based on a cohort of SSc patients with demographic information, clinical data, and preoperative chest CT scans who underwent LTx between 2004 and 2020. This cohort consists of 102 patients (mean age, 50 years ± 10, 61% (62/102) females). Five CT-derived body composition features (bone, skeletal muscle, visceral, subcutaneous, and intramuscular adipose tissues) and three CT-derived cardiopulmonary features (heart, arteries, and veins) were automatically computed using 3-D convolutional neural networks. Cox regression was used to identify post-LTx survival factors, generate composite prediction models, and stratify patients based on mortality risk. Model performance was assessed using the area under the receiver operating characteristics curve (ROC-AUC). Muscle mass ratio, bone density, artery-vein volume ratio, muscle volume, and heart volume ratio computed from CT images were significantly associated with post-LTx survival. Models using only CT-derived features outperformed all state-of-the-art clinical models in predicting post-LTx survival. The addition of CT-derived features improved the performance of traditional models at 1-year, 3-year, and 5-year survival prediction with maximum AUC scores of 0.77 (0.67-0.86), 0.85 (0.77-0.93), and 0.90 (95% CI: 0.83-0.97), respectively. The integration of CT-derived features with demographic and clinical features can significantly improve t post-LTx survival prediction and identify high-risk SSc patients. Question What CT features can predict post-lung-transplant survival for SSc patients? Finding CT body composition features such as muscle mass, bone density, and cardiopulmonary volumes significantly predict survival. Clinical relevance Our individualized risk assessment tool can better guide clinicians in choosing and managing patients requiring lung transplant for systemic sclerosis.

Systemic immunity-inflammation index is associated with body fat distribution among U.S. adults: evidence from national health and nutrition examination survey 2011–2018

ObjectiveThe systemic immunity-inflammation index (SII) is a newly developed biomarker that provides an integrated measure of inflammation in the body. We aim to evaluate the relationship between SII and body fat distribution.MethodsAdults from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 were included. The SII was computed using lymphocyte (LC), neutrophil (NC), and platelet (PC) counts as its components. Body fat distribution was assessed by (total, android, gynoid) percentage fat, total abdominal fat area, subcutaneous adipose tissue area, visceral adipose tissue area, and the ratio of visceral to subcutaneous adipose tissue area (V/S ratio). Multivariable weighted linear regression and subgroup analysis were use to examine the relationships between fat distribution and SII. Restricted cubic splines (RCS) and threshold effect analysis were used to examine analyze nonlinear associations.ResultsAfter exclusions, a total of 11,192 adults with a weighted mean age of 38.46 ± 0.26 years were studied. In multivariable weighted linear regression, each level increase in log2SII was associated with increased of 0.23 SDs total percentage fat (95% CI = 0.03, 0.43) and 0.26 SDs android percentage fat (95% CI = 0.06, 0.47). Besides, the subgroup analysis showed that the positive association between SII and android percentage fat was mainly among obese individuals (BMI > 30 kg/m2) and non-obese individuals without DM or hypertension. Meanwhile, the relationship between SII and the V/S ratio was found to be significant in the female subgroup, the obese subgroup, individuals with non-alcoholic fatty liver disease (NAFLD), and those without diabetes mellitus. Finally, SII exhibited an inverted U-shaped relationship with total percentage fat, android percent fat and total abdominal fat. Accordingly, threshold effect analysis indicated a positive association between lower SII levels and total percentage fat, android percentage fat and total abdominal fat area.ConclusionsIn the nationwide study, it was observed that the SII exhibited a significant correlation with higher levels of body fat, specifically android fat. This association was particularly noticeable within specific subgroups of the population.

Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics

BackgroundCancer cachexia (CCx) presents a multifaceted challenge characterized by negative protein and energy balance and systemic inflammatory response activation. While previous CCx studies predominantly focused on mouse models or human body fluids, there's an unmet need to elucidate the molecular inter-organ cross-talk underlying the pathophysiology of human CCx. MethodsSpatial metabolomics were conducted on liver, skeletal muscle, subcutaneous and visceral adipose tissue, and serum from cachectic and control cancer patients. Organ-wise comparisons were performed using component, pathway enrichment and correlation network analyses. Inter-organ correlations in CCx altered pathways were assessed using Circos. Machine learning on tissues and serum established classifiers as potential diagnostic biomarkers for CCx. ResultsDistinct metabolic pathway alteration was detected in CCx, with adipose tissues and liver displaying the most significant (P ≤ 0.05) metabolic disturbances. CCx patients exhibited increased metabolic activity in visceral and subcutaneous adipose tissues and liver, contrasting with decreased activity in muscle and serum compared to control patients. Carbohydrate, lipid, amino acid, and vitamin metabolism emerged as highly interacting pathways across different organ systems in CCx. Muscle tissue showed decreased (P ≤ 0.001) energy charge in CCx patients, while liver and adipose tissues displayed increased energy charge (P ≤ 0.001). We stratified CCx patients by severity and metabolic changes, finding that visceral adipose tissue is most affected, especially in cases of severe cachexia. Morphometric analysis showed smaller (P ≤ 0.05) adipocyte size in visceral adipose tissue, indicating catabolic processes. We developed tissue-based classifiers for cancer cachexia specific to individual organs, facilitating the transfer of patient serum as minimally invasive diagnostic markers of CCx in the constitution of the organs. ConclusionsThese findings support the concept of CCx as a multi-organ syndrome with diverse metabolic alterations, providing insights into the pathophysiology and organ cross-talk of human CCx. This study pioneers spatial metabolomics for CCx, demonstrating the feasibility of distinguishing cachexia status at the organ level using serum.

Associations between visceral and liver fat and cardiac structure and function: a UK Biobank study.

Different fat depots have connected to cardiovascular health. We assessed the associations of abdominal magnetic resonance-quantified visceral adipose tissue (VAT) and liver fat (proton density fat fraction, PDFF) with cardiac magnetic resonance (CMR)-measured cardiac structure and function, and considered potential mechanism. Our study encompassed 10,920 participants from the UK Biobank. We utilized multiple linear regression and multiple mediation analyses to estimate the connections between VAT or PDFF and CMR metrics. Elevated VAT or PDFF exhibited associations with adverse left ventricular (LV) structure (increased wall thickness, concentric LV remodeling), impaired LV function (lower LV global functional index, absolute value of LV global longitudinal strain), and diminished left atrial volumes and stroke volume (all p-values were significant）. Upon stratifying participants based on VAT and PDFF combinations, all groups, except the low VAT-low PDFF group, were linked to unfavorable cardiac remodeling metrics. The high VAT-high PDFF group displayed the most pronounced cardiac alterations. Multiple mediation analyses were employed to investigate potential mediating roles of systolic blood pressure (SBP), diabetes, dyslipidemia and blood biomarkers (lipidemia, transaminases) in the adipose-CMR relationship. The findings suggested that VAT or PDFF was related to SBP, diabetes, dyslipidemia, lipid profile, liver function, and glucose. Several potential mediating pathways were identified, primarily through SBP and triglyceride-glucose index, which only partially explained the adipose-CMR relationship. We established the independent associations of VAT and PDFF with unhealthy cardiac structure and function. Furthermore, it identifies SBP and insulin resistance as important mediating factors.

Physical activity and sedentary behaviour in relation to body composition, estimated insulin sensitivity and arterial stiffness in adults with type 1 diabetes

AimsTo examine the association of daily PA levels and sedentary behaviour with body composition, estimated insulin sensitivity, and arterial stiffness in adults with type 1 diabetes (T1D). MethodsCross-sectional study in adults with T1D (n = 54). PA levels (daily steps, and time in moderate-to-vigorous intensity PA (MVPA)) and sedentary behaviour were measured using accelerometry for 7 days (McRoberts® DynaPort MoveMonitor). Cardiopulmonary exercise test for VO2max. Anthropometrics were collected, and body composition (total and % of fat mass (FMtot, FM%), total and % of lean mass (LMtot, LM%), and estimated visceral adipose tissue (VAT)) volume was assessed with dual energy X-ray-absorptiometry (DXA). Estimates of insulin sensitivity were determined (estimated glucose disposal rate (eGDR) and total daily insulin dose). Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV (m/s); SphygmoCor®). ResultsLower 10-years HbA1c associated moderately with all PA measures. Favourable moderate associations were also found between PA measures and BMI, waist, VAT but not FM and LM. PA measures were favourably associated with a lower total daily insulin dose and higher eGDR. All PA parameters associated moderately with cf-PWV however not independent from traditional risk factors. VO2max was inversely associated with cf-PWV independent of age, T1D duration and 24-hour mean blood pressure. ConclusionsHigher levels of PA, lower sedentary behaviour and greater exercise capacity are favourably associated with long-term glycaemic control, body composition, insulin dosage, estimated insulin sensitivity and arterial stiffness in adults with T1D. Therefore, regular PA and limiting sedentary time should be encouraged to improve metabolic and cardiovascular health in this population. Future longitudinal studies should explore mutual interactions and synergistic effects of PA on these outcomes.

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity

ObjectiveObesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes. MethodsThe expression of the NPY/melanocortin receptors’ levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system. ResultsIn this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity. ConclusionsOur results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.

External validation of a deep learning model for automatic segmentation of skeletal muscle and adipose tissue on abdominal computed tomography images.

Body composition assessment using computed tomography (CT) images at the L3-level is increasingly applied in cancer research. Robust high-throughput automated segmentation is key to assess large patient cohorts and to support implementation of body composition analysis into routine clinical practice. We trained and externally validated a deep learning neural network (DLNN) to automatically segment L3-CT images. Expert-drawn segmentations of visceral and subcutaneous adipose tissue (VAT/SAT) and skeletal muscle (SM) of L3-CT-images of 3,187 patients undergoing abdominal surgery were used to train a DLNN. The external validation cohort was comprised of 2,535 patients with abdominal cancer. DLNN performance was evaluated with (geometric) Dice Similarity (DS) and Lin's Concordance Correlation Coefficient. There was a strong concordance between automatic and manual segmentations with median DS for SM, VAT, and SAT of 0.97 (interquartile range, IQR: 0.95-0.98), 0.98 (IQR: 0.95-0.98), and 0.95 (IQR: 0.92-0.97), respectively. Concordance correlations were excellent: SM 0.964 (0.959-0.968), VAT 0.998 (0.998-0.998), and SAT 0.992 (0.991-0.993). Bland-Altman metrics indicated only small and clinically insignificant systematic offsets; SM radiodensity: 0.23 hounsfield units (0.5%), SM: 1.26 cm2.m-2 (2.8%), VAT: -1.02 cm2.m-2 (1.7%), and SAT: 3.24 cm2.m-2 (4.6%). A robustly-performing and independently externally validated DLNN for automated body composition analysis was developed. CT-based body composition analysis is highly prognostic for long-term overall survival in oncology. This DLNN was succesfully trained and externally validated on several large patient cohorts and will therefore enable large scale population studies and implementation of body composition analysis into clinical practice.

Accelerated BDNF expression in visceral white adipose tissues following high-fat diet feeding in mice.

Brain-derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high-fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia-inducible factor 1α (Hif1α) and platelet-derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti-inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues.

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.

Effect of sarcopenia on liver cirrhosis with complicating oesophageal and gastric varices after endoscopic therapy

Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4 %) was significantly lower than that in patients with LC-EGVB (41.2 %). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic β cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

A 2-year follow-up to a randomized controlled trial on resistance training in postmenopausal women: vasomotor symptoms, quality of life and cardiovascular risk markers

BackgroundMost women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women.MethodsThis observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT.ResultsAlthough all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p < 0.001 and p = 0.006, respectively) regarding MS-VMS. The IG maintained a significantly lower MS-VMS frequency than the CG at the 6-month follow-up. At the 2-year follow-up, there was no significant difference between the original RCT groups. No significant changes over time or differences between groups were found in HRQoL or cardiovascular risk markers. However, significant interactions between original RCT groups and time were found for visceral adipose tissue (p = 0.041), ferritin (p = 0.045), and testosterone (p = 0.010).ConclusionsA 15-week resistance training intervention reduced MS-VMS frequency up to six months post-intervention compared to a CG, but the effect was not maintained after two years. The RTI did neither contribute to preserved improvements of cardiovascular risk markers nor improved HRQoL after two years compared to a CG.Trial registrationClinical trials.gov registered ID: NCT01987778, trial registration date 2013–11-19.

Chronic intermittent hypoxia triggers cardiac fibrosis: Role of epididymal white adipose tissue senescent remodeling?

Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter-organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling. In a first experiment, 10-week-old C57bl6J male mice (n = 10/group) were exposed to 14 days of CIH (8 h daily, 5%-21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild-type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT-qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy. CIH-induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH-induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH-induced myocardial fibrosis. Short-term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA-related cardiac disorders.