Subcutaneous Adipose Tissue Research Articles

Body composition as a determinant of the therapeutic index with androgen signaling inhibition.

Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC). A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma. Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48). Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI.

Age-adjusted Charlson comorbidity index and its association with body composition and overall survival in patients with colorectal cancer.

To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). In this cohort study, patients (≥ 18years old) with CRC were followed for 36months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.

Visceral fat mass dynamics in a 2-year randomized STrength versus ENdurance training trial in people with obesity.

To compare the effectiveness of strength versus endurance training on reducing visceral fat in individuals with obesity. For the STrength versus ENdurance (STEN) 24-month randomized clinical trial, we assigned 239 participants with abdominal obesity to either strength or endurance training (two to three times a week, 60 min/training session) in addition to standard nutritional counselling to promote a healthy diet. Changes in abdominal visceral adipose tissue (VAT) area quantified by magnetic resonance imaging after 12 months were defined as a primary endpoint. Participants (aged 44 years, 74% women, body mass index: 37 kg/m2, mean VAT volume: 4050 cm3) had an approximately 50% retention rate and a 30% good training programme adherence at 12 months. There was no difference between strength and endurance training in VAT volume dynamics after 12 and 24 months (p = .13). Only in the good adherence group did we find a trend for reduced VAT volume in both training regimens. Independently of the exercise programme, there was a continuous trend for moderate loss of abdominal subcutaneous AT volume, body fat mass, body mass index and improved parameters of insulin sensitivity. Although parameters of physical fitness improved upon both exercise interventions, the dynamics of resting energy expenditure, glucose and lipid metabolism parameters were not different between the intervention groups and did not significantly improve during the 2-year trial (p > .05). Despite heterogeneous individual training responses, strength and endurance training neither affected VAT volume nor key secondary endpoints differently.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower visceral and hepatic lipid content in recent-onset type 1 diabetes and type 2 diabetes.

To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes. In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis. A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm3). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm3) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes. A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR.

The therapeutic effect of NRF2 activator, ezetimibe, in cardiac cachexia.

Heart failure (HF) is caused by functional and structural irregularity leading to impaired ejection or filling capacity of the heart. HF leads to chronic inflammatory conditions in the heart leads to weight loss, anorexia, and muscle atrophy known as cachexia. The present study was carried out to investigate the role of Ezetimibe, an NRF2 activator, in cardiac cachexia and to develop a treatment strategy for cardiac cachexia. Balb/c mice of either sex at 6-8 weeks of age were given 2 mg/kg of doxorubicin in 0.9% sodium chloride solution intraperitoneally (i.p.) for the alternate days for the first week and then once a week for the next 4 weeks. After induction of cardiac atrophy, treatment with Ezetimibe (1.5 mg/kg, p.o) was given for the next 4 weeks. In the cardiac cachectic animals, a significant decrease in body weight, food, and water intake was observed. Cardiac cachectic animals showed a significant increase in serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH, and CRP levels. Cardiac atrophic index, heart weight to body weight ratios (HW/BW), right ventricular weight to heart weight ratios (RV/HW), and left ventricular weight to heart weight ratios (LV/HW), were significantly decreased in cardiac cachectic animals. The weights of the skeletal muscles such as EDL, gastrocnemius, soleus, tibialis anterior, and quadriceps muscles, and the weight of adipose tissue such as subcutaneous, visceral, perirenal, and brown adipose tissue were significantly decreased in the cardiac cachectic group relative to the normal group. Treatment with ezetimibe improves body weight, food intake, and water intake. Ezetimibe decreases serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK-MB, LDH and CRP levels. Cardiac atrophic markers such as HW/BW, RV/HW, and LV/HW were improved. The weight of skeletal muscles and adipose tissue was increased after treatment with ezetimibe. Our data showed that the NRF2 activator, Ezetimibe produces a beneficial effect on cardiac cachexia in the doxorubicin-induced cardiac cachexia model. Ezetimibe was successful to reduce the levels of inflammatory cytokines, ameliorate the effects on cardiac muscle wasting, lipid levels, fat tissues, and skeletal muscles.

Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma.

The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear. Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT. Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16mmol/L decrease in HDL-C and a 0.18g/L decrease in ApoA1. Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.

Blood methylation pattern reflects epigenetic remodelling in adipose tissue after bariatric surgery

Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood. Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N=6 female) with severe obesity pre- and post-surgery. The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from-11.5 to 10.8%; OVAT: 14,632 DMRs from-13.7 to 12.8%) than in blood (9267 DMRs from-8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery. Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors AT's inflammatory state post-bariatric surgery. The funding sources are listed in the Acknowledgments section.

Convolutional Neural Network-Based Automated Segmentation of Skeletal Muscle and Subcutaneous Adipose Tissue on Thigh MRI in Muscular Dystrophy Patients.

We aim to develop a deep learning-based algorithm for automated segmentation of thigh muscles and subcutaneous adipose tissue (SAT) from T1-weighted muscle MRIs from patients affected by muscular dystrophies (MDs). From March 2019 to February 2022, adult and pediatric patients affected by MDs were enrolled from Azienda Ospedaliera Universitaria Pisana, Pisa, Italy (Institution 1) and the IRCCS Stella Maris Foundation, Calambrone-Pisa, Italy (Institution 2), respectively. All patients underwent a bilateral thighs MRI including an axial T1 weighted in- and out-of-phase (dual-echo). Both muscles and SAT were manually and separately segmented on out-of-phase image sets by a radiologist with 6 years of experience in musculoskeletal imaging. A U-Net1 and U-Net3 were built to automatically segment the SAT, all the thigh muscles together and the three muscular compartments separately. The dataset was randomly split into the on train, validation, and test set. The segmentation performance was assessed through the Dice similarity coefficient (DSC). The final cohort included 23 patients. The estimated DSC for U-Net1 was 96.8%, 95.3%, and 95.6% on train, validation, and test set, respectively, while the estimated accuracy for U-Net3 was 94.1%, 92.9%, and 93.9%. Both of the U-Nets achieved a median DSC of 0.95 for SAT segmentation. The U-Net1 and the U-Net3 achieved an optimal agreement with manual segmentation for the automatic segmentation. The so-developed neural networks have the potential to automatically segment thigh muscles and SAT in patients affected by MDs.

High-Intensity Focused Ultrasound Increases Facial Adipogenesis in a Swine Model via Modulation of Adipose-Derived Stem Cell Cilia.

Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine (n = 2) via modulation of ASC cilia. Expression of CD166, an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor (AURKA), and increased expression of a cilia increasing factor (ARL13B) and PPARG and CEBPA, which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.

Dynamics of single-nuclei transcriptomic profiling of adipose tissue from diverse anatomical locations during mouse aging process

Adipose tissue plays critical roles in an individual’s aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell–cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.

Effects of moderate/vigorous activity on 3-year body composition changes in postmenopausal women: a target trial emulation.

Background and Objective Postmenopausal women tend to experience significant changes in body composition, particularly abdominal adipose tissue (AAT) deposition patterns, which are hypothesized to be critical factors influencing future cardiometabolic disease risk. Physical activity has a demonstrable effect on body composition and overall health. However, there is little evidence for how different intensities and durations of physical activity over a sustained period of time influence AAT patterns and other measures of body composition in postmenopausal women. We emulated a target trial of physical activity interventions, including the 2018 Physical Activity Guidelines for Americans recommendations, on 3-year changes in AAT and body composition. Methods We analyzed observational data from 4,451 postmenopausal women aged 50-79 years in the Women's Health Initiative (WHI) to emulate a three-year target trial of adhering to increasing minutes of moderate (at least 15, 30, 75, 150, 300 minutes/week) and vigorous (at least 15, 30, 75, 150 minutes/week) physical activity aligned with the physical activity guidelines. All participants had repeated whole body Dual X-Ray Absorptiometry (DXA) scans with derived abdominal visceral (VAT) and subcutaneous adipose tissue (SAT). The measured differences in average levels of VAT, SAT, and other body composition measures determined at end of follow-up were estimated with the parametric-g formula. Results Over 3 years, interventions of increasing minutes of moderate activity would result in dose-dependent reductions in abdominal VAT, SAT, and overall body fat, and increases in lean soft tissue, with the greatest estimated benefit at the 2018 physical activity guideline recommendation of 150 mins/wk or more. Compared to no intervention, if all participants had adhered to at least 150 mins/wk of moderate physical activity, they would have 16.8 cm2 lower VAT (95% CI -23.1, -10.4), 26.8 cm2 lower SAT (95% CI -36.3, -17.3), 1.3% lower total body fat% (95% CI -1.8, -0.7), 1.2 % higher total lean soft tissue% (95% CI 0.7, 1.8), and 2.6 kg lower total bodyweight (95% CI -3.6, -1.5). We saw similar patterns in our vigorous-intensity activity interventions - if all participants adhered to at least 150 mins/wk, they would have experienced 6.7 cm2 lower VAT (95% CI -17.7, 4.3), 13.3 cm2 lower SAT (95% CI -28.8, 2.1), 1.0 % lower total body fat percent (95% CI -2.0, 0.0 ), % higher total lean soft tissue percent (95% CI) and a 0.9 kg lower total bodyweight (95% CI -2.7, 0.8). Conclusion This hypothetical emulated intervention indicated that postmenopausal women who adhere to physical activity guideline recommendations would experience beneficial changes in abdominal VAT, SAT, and overall body composition over 3 years. The study results underscore the imperative to explore further how physical activity may serve as a potential determinant of body composition.

Prediction of visceral adipose tissue magnitude using a new model based on simple clinical measurements.

Waist circumference (WC) is a reliable obesity surrogate but may not distinguish between visceral and subcutaneous adipose tissue. Our aim was to develop a novel sex-specific model to estimate the magnitude of visceral adipose tissue measured by computed tomography (CT-VAT). The model was initially formulated through the integration of anthropometric measurements, laboratory data, and CT-VAT within a study group (n=185), utilizing the Multivariate Adaptive Regression Splines (MARS) methodology. Subsequently, its correlation with CT-VAT was examined in an external validation group (n=50). The accuracy of the new model in estimating increased CT-VAT (>130 cm2) was compared with WC, body mass index (BMI), waist-hip ratio (WHR), visceral adiposity index (VAI), a body shape index (ABSI), lipid accumulation product (LAP), body roundness index (BRI), and metabolic score for visceral fat (METS-VF) in the study group. Additionally, the new model's accuracy in identifying metabolic syndrome was evaluated in our Metabolic Healthiness Discovery Cohort (n=430). The new model comprised WC, gender, BMI, and hip circumference, providing the highest predictive accuracy in estimating increased CT-VAT in men (AUC of 0.96 ± 0.02), outperforming other indices. In women, the AUC was 0.94 ± 0.03, which was significantly higher than that of VAI, WHR, and ABSI but similar to WC, BMI, LAP, BRI, and METS-VF. It's demonstrated high ability for identifying metabolic syndrome with an AUC of 0.76 ± 0.03 (p<0.001). The new model is a valuable indicator of CT-VAT, especially in men, and it exhibits a strong predictive capability for identifying metabolic syndrome.

Single nucleus RNA-sequencing integrated into risk variant colocalization discovers 17 cell-type-specific abdominal obesity genes for metabolic dysfunction-associated steatotic liver disease

Abdominal obesity increases the risk for non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). To elucidate the directional cell-type level biological mechanisms underlying the association between abdominal obesity and MASLD, we integrated adipose and liver single nucleus RNA-sequencing and bulk cis-expression quantitative trait locus (eQTL) data with the UK Biobank genome-wide association study (GWAS) data using colocalization. Then we used colocalized cis-eQTL variants as instrumental variables in Mendelian randomization (MR) analyses, followed by functional validation experiments on the target genes of the cis-eQTL variants. We identified 17 colocalized abdominal obesity GWAS variants, regulating 17 adipose cell-type marker genes. Incorporating these 17 variants into MR discovers a putative tissue-of-origin, cell-type-aware causal effect of abdominal obesity on MASLD consistently with multiple MR methods without significant evidence for pleiotropy or heterogeneity. Single cell data confirm the adipocyte-enriched mean expression of the 17 genes. Our cellular experiments across human adipogenesis identify risk variant -specific epigenetic and transcriptional mechanisms. Knocking down two of the 17 genes, PPP2R5A and SH3PXD2B, shows a marked decrease in adipocyte lipidation and significantly alters adipocyte function and adipogenesis regulator genes, including DGAT2, LPL, ADIPOQ, PPARG, and SREBF1. Furthermore, the 17 genes capture a characteristic MASLD expression signature in subcutaneous adipose tissue. Overall, we discover a significant cell-type level effect of abdominal obesity on MASLD and trace its biological effect to adipogenesis. NIH grants R01HG010505, R01DK132775, and R01HL170604; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant No. 802825), Academy of Finland (Grants Nos. 333021), the Finnish Foundation for Cardiovascular Research the Sigrid Jusélius Foundation and the Jane and Aatos Erkko Foundation; American Association for the Study of Liver Diseases (AASLD) Advanced Transplant Hepatology award and NIH/NIDDK (P30DK41301) Pilot and Feasibility award; NIH/NIEHS F32 award (F32ES034668); Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2021), the Academy of Finland grant (Contract no. 138006); Academy of Finland (Grant Nos 335443, 314383, 272376 and 266286), Sigrid Jusélius Foundation, Finnish Medical Foundation, Finnish Diabetes Research Foundation, Novo Nordisk Foundation (#NNF20OC0060547, NNF17OC0027232, NNF10OC1013354) and Government Research Funds to Helsinki University Hospital; Orion Research Foundation, Maud Kuistila Foundation, Finish Medical Foundation, and University of Helsinki.

A Single Injection of ADRCs Does Not Prevent AAA Formation in Rats in a Randomized Blinded Design.

There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation and preserve vascular integrity, potentially slowing the progression of AAA. In our study, subcutaneous adipose tissue was harvested from male Sprague Dawley rats, from which ADRCs were isolated. AAA was induced in these rats using intraluminal porcine pancreatic elastase, followed by intravenous administration of either ADRCs (106 cells) or saline (0.1 mL). We monitored the progression of AAA through weekly ultrasound, and the rats were sacrificed on day 28 for histological analysis. Our results showed no significant difference in the inner abdominal aortic diameter at day 28 between the control group (172% ± 73%, n = 17) and the ADRC-treated group (181% ± 75%, n = 15). Histological analyses of AAA cross-sections also revealed no significant difference in the infiltration of neutrophils or macrophages between the two groups. Furthermore, the integrity and content of elastin in the tunica media were similar between groups. These findings indicate that a single injection of ADRCs does not inhibit the development of AAA in rats in a randomized blinded study.

Associations between adrenal gland volume and adipose tissue compartments – a whole body MRI study

BackgroundObesity is associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Effects of glucocorticoids on adipose tissues appear to depend on the specific adipose depot, in which they take place. In this study, we aimed to investigate the role of MRI-based adrenal gland volume as an imaging marker in association with different adipose tissue compartments.MethodsThe study cohort derives from the population-based research platform KORA (Cooperative Health Research in the Augsburg Region, Germany) MRI sub-study, a cross-sectional sub-study investigating the interactions between subclinical metabolic changes and cardiovascular disease in a study sample of 400 participants. Originally, eligible subjects underwent a whole-body MRI. MRI-based segmentations were performed manually and semi-automatically for adrenal gland volume, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epi- and pericardial fat and renal sinus fat. Hepatic and pancreatic lipid content were measured as pancreatic proton density fraction (PDFF) and MR-spectroscopic hepatic fat fraction (HFF). Multivariable linear regression analyses were performed.ResultsA number of 307 participants (56.2 ± 9.1 years, 60.3% male, 14.3% with type 2 diabetes (T2DM), 30.6% with obesity, 34.2% with hypertension) were included. In multivariable analyses, strong positive associations between adrenal gland volume and VAT, total adipose tissue (TAT) as well as HFF persisted after extensive step-wise adjustment for possible metabolic confounders (VAT: beta = 0.31, 95%-CI [0.71, 0.81], p < 0.001; TAT: beta = 0.14, 95%-CI [0.06, 0.23], p < 0.001; HFF: beta = 1.17, 95%-CI [1.04, 1.31], p = 0.009). In contrast, associations between adrenal gland volume and SAT were attenuated in multivariate analysis after adjusting for BMI. Associations between pancreatic PDFF, epi- and pericardial fat and renal sinus fat were mediated to a great extent by VAT (pancreatic PDFF: 72%, epicardial adipose tissue: 100%, pericardial adipose tissue: 100%, renal sinus fat: 81.5%).ConclusionOur results found MRI-based adrenal gland volume as a possible imaging biomarker of unfavorable adipose tissue distribution, irrespective of metabolic risk factors. Thus, adrenal gland volume may serve as a potential MRI-based biomarker of metabolic changes and contributes to an individual characterization of metabolic states and individual risk stratification. Future studies should elucidate in a longitudinal study design, if and how HPA axis activation may trigger unfavorable adipose tissue distribution and whether and to which extent this is involved in the pathogenesis of manifest metabolic syndrome.

Comparison of the infrapatellar and subcutaneous adipose tissue biopsy material as a source of mesenchymal stromal cells for regenerative medicine in traumatology

Objective. The use of infrapatellar fat pad (IPFP) as the source of mesenchymal stem cells (MSCs), show an age-independent proliferation and differentiation potential. In addition, the pronounced chondrogenic potential of IPFP-ASCs makes them promising candidates for research for use in other methodsof regenerative therapy. Methods. A direct immunohistochemical study was carried out in serial paraffin sections of the biopsy material of Hoffa`s fat pad and subcutaneus fat tissue, using monoclonal antibodies. The minimum criteria established by the International Society for Cell Therapy to ensure the identity of MSCs use CD73 and CD105 as positive markers and CD34, CD31, CD45 as a negative. Results. According to the results of histological, immunohistochemical, morphometric and statistical studies, it was found that in the biopsy of both tissues the relative number of cells with an immunoprofile CD105+, CD73+, CD34–, CD31–, CD45– in the standard field of view (×200) was: 7.25 (5.42; 8.89 ) %, and 11.11 (8.46; 13.45) %, no statistically significant difference was found between comparison groups (р &gt; 0,05). Conclusion. The therapeutic effect of mesenchymal stem cells of subcutaneous adipose tissue has been proven, thus the identification of similar cells in the biopsy material and relatively similar density in the Hoffa body makesit an important source of adipose-derived stem cells that can be used for regenerative engineering tissue.

Micromassage Compression Leggings Associated with Physical Exercise: Pilot Study and Example of Evaluation of the Clinical and Instrumental Effectiveness of Conservative Treatment in Lipedema.

We evaluated the effect of compression leggings with micromassage in association with physical activity on women with lipedema, not previously treated and without recent changes in body weight. The treatment resulted in an improvement in all subjective parameters, in spontaneous and evoked pain, in the volume of the limbs, in the absence of significant changes in body weight, and regardless of the duration of use, age, years of illness, the clinical stage, and body mass index (BMI). Evoked pain did not improve in areas affected by untreated lipedema; foot circumferences did not increase. We found a significant reduction in the thickness of subcutaneous adipose tissue (SAT) and skin evaluated in multiple points of the lower limb. Micromassage compression leggings are proposed as an integral part of conservative treatment. A method is proposed for the clinical evaluation of evoked pain, called the Progressive Pain Check (PPC), which allows for the calculation of a numerical score called the Ricolfi-Patton Score (RPS) and for the ultrasound evaluation of tissues. The method is simple and repeatable and allows for completion of the clinical evaluation of the patient at diagnosis and for an evaluation of the effects of various treatments, even applied to just one side of the body.

Effects of altering the ratio of C16:0 and cis-9 C18:1 in rumen bypass fat on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls

BackgroundC16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo. This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls. Thirty finishing Angus bulls (626 ± 69 kg, 21 ± 0.5 months) were divided into 3 treatments according to the randomized block design: (1) control diet without additional fat (CON), (2) CON + 2.5% palmitic acid calcium salt (PA, 90% C16:0), and (3) CON + 2.5% mixed fatty acid calcium salt (MA, 60% C16:0 + 30% cis-9 C18:1). The experiment lasted for 104 d, after which all the bulls were slaughtered and sampled for analysis.ResultsMA tended to reduce 0–52 d dry matter intake compared to PA (DMI, P = 0.052). Compared with CON and MA, PA significantly increased 0–52 d average daily gain (ADG, P = 0.027). PA tended to improve the 0–52 d feed conversion rate compared with CON (FCR, P = 0.088). Both PA and MA had no significant effect on 52–104 days of DMI, ADG and FCR (P > 0.05). PA tended to improve plasma triglycerides compared with MA (P = 0.077), significantly increased plasma cholesterol (P = 0.002) and tended to improve subcutaneous adipose weight (P = 0.066) when compared with CON and MA. Both PA and MA increased visceral adipose weight compared with CON (P = 0.021). Only PA increased the colonization of Rikenellaceae, Ruminococcus and Proteobacteria in the cecum, and MA increased Akkermansia abundance (P < 0.05). Compared with CON, both PA and MA down-regulated the mRNA expression of Claudin-1 in the jejunum (P < 0.001), increased plasma diamine oxidase (DAO, P < 0.001) and lipopolysaccharide (LPS, P = 0.045). Compared with CON and MA, PA down-regulated the ZO-1 in the jejunum (P < 0.001) and increased plasma LPS-binding protein (LBP, P < 0.001). Compared with CON, only PA down-regulated the Occludin in the jejunum (P = 0.013). Compared with CON, PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose (P < 0.001) and increased plasma IL-6 (P < 0.001). Compared with CON, only PA up-regulated the TNF-α in the visceral adipose (P = 0.01). Compared with CON and MA, PA up-regulated IL-6 in the visceral adipose (P < 0.001), increased plasma TNF-α (P < 0.001), and reduced the IgG content in plasma (P = 0.035). Compared with CON, PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle (P < 0.05), while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1. However, neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON (P > 0.05).ConclusionsMA containing 30% cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity, adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization, improving colonization of Akkermansia, reducing intestinal barrier damage, and down-regulating NF-κB activation.

The Effect of Subclinical Ketosis on the Peripheral Blood Mononuclear Cell Inflammatory Response and Its Crosstalk with Depot-Specific Preadipocyte Function in Dairy Cows.

During the periparturient period, cows undergo heightened energy demands at lactation onset, paired with reduced dry matter intake, leading to negative energy balance (NEB). Excessive lipolysis-driven adipose tissue remodeling, triggered by NEB, significantly contributes to ketosis in periparturient dairy cows. However, the role of peripheral blood mononuclear cells (PBMCs) in the pathogenesis of ketosis and in modulating adipose tissue function remains poorly understood. Here, we investigated how ketosis affects the transcriptional profile and secretome of PBMCs and its influence on preadipocyte function in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Twenty-one postpartum Holstein dairy cows were categorized as either subclinical ketosis (SCK; BHB ≥ 1.0 mM) or control (CON; BHB < 0.8 mM) based on blood beta-hydroxybutyrate (BHB) concentration screening. Blood samples were collected intravenously for the isolation of PBMCs and serum metabolic profiling. Ketosis elevated circulating NEFA and BHB levels but reduced total WBC and neutrophil counts. Isolated PBMCs were evaluated for gene expression and used to produce conditioned media (PBMC-CM), during which PBMCs were stimulated with 10 ng/mL LPS. The overall phenotype of PBMCs was largely consistent between SCK and CON cows, with minimal differences detected in immunomodulatory cytokine expression and PBMC-CM composition following stimulation. Preadipocytes isolated from non-ketotic cows were treated with PBMC-CM to assess the effect of PBMC secretomes on adipose cell function. Preadipocytes treated with SCK PBMC-CM showed reduced lipid accumulation compared to those treated with CON PBMC-CM regardless of the depot. SAT preadipocytes had heightened expression of lipid metabolism-related genes, including DGAT1, LIPE, and FASN, compared to VAT when treated with SCK PBMC-CM. Preadipocytes treated with CM from PBMC stimulated by LPS exhibited upregulation in IL1B and IL6 regardless of the depot or source of PBMCs. Together, these results indicate that although PBMC profiles showed minimal differences, preadipocytes treated with PBMC-CM may be influenced by additional factors, leading to altered preadipocyte function and gene expression that may contribute to adipose cellular dysfunction.

Treatment of HER2-positive cutaneous apocrine carcinoma of the axilla.

Cutaneous apocrine carcinoma (CAC) is an extremely rare skin appendage malignant tumor that develops in the apocrine sweat glands, and no evidence-based drug therapy has been established. A 61-year-old female patient was diagnosed with axillary CAC with axillary lymph node metastasis and underwent surgery. Pathological examination revealed seven lymph node metastases. Immunostaining revealed that the tumor cells were estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)-positive. The patient received chemotherapy, including anti-HER2 drugs, and hormone therapy to prevent recurrence. No recurrence was observed for > 3years after surgery. The apocrine glands in the skin and mammary glands have similar characteristics and mammary glands are thought to be modified or derived from the apocrine glands present in the subcutaneous adipose tissue. Therefore, ER, PgR, and HER2 levels may be positive in CAC. Drug treatments for breast cancer may also be effective for CAC.