Deep Subcutaneous Adipose Tissue Research Articles

Analysis of Physiological Oxygen Concentrations in Different Abdominal Fat Layers by Body Mass Index.

Physiological oxygen concentration in adipose tissue is closely linked to metabolic disorders such as chronic inflammation and insulin resistance. However, the nature of the variation in the oxygen levels of adipose tissue with body mass index (BMI) and depths of abdominal fat remain unclear. Therefore, this study aimed to elucidate the patterns of oxygen concentration in adipose tissue layers according to BMI. In this study, patients undergoing abdominal fat removal surgery were divided into the normal-weight (NW) or overweight-obese (OW) groups based on their BMI. Oxygen concentrations in abdominal superficial (sSAT) and deep subcutaneous adipose tissue (dSAT) were measured. The oxygen consumption rate, mean cell area, and capillary density in both tissue layers were compared between the two groups. Furthermore, the interaction between these three variables, BMI, and adipose tissue oxygen concentration, was analyzed using linear regression. A total of 42 patients were recruited in this study and we observed that oxygen concentration in the sSAT was significantly lower than in the dSAT, irrespective of BMI. In terms of the oxygen concentration in the dSAT, OW's was significantly lower than that of NW's. Linear regression analysis revealed a significant correlation between dSAT oxygen concentration and BMI, mean adipocyte area, and vascular density. Individuals who are obese have significantly lower oxygen levels in the deep abdominal adipose tissue, and this is influenced by BMI, adipocyte area, and capillary density. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Choke Anastomosis: A Key Element Acting as a Shunt Converter Between Adjacent Angiosomes.

Choke anastomosis is commonly recognized as a resistance factor that detrimentally affects the hemodynamics of the skin flap; however, its additional potential physiological roles in normal skin function are currently not fully understood. Ten cadaveric forehead flap specimens pedicled with unilateral STAs were perfused with lead oxide-gelatin mixture, and then dissected into 3 layers, including the super temporal fascia-frontalis-galea aponeurotica layer, the subcutaneous adipose tissue layer, and the "super-thin flap" layer. The forehead flap and stratified specimens underwent molybdenum target x-ray and subsequent transparent processing to effectively visualize the microscopic spatial architecture of arterial vessels across all levels. Based on the different anastomoses near the midline area of the flap, 2 types of arterial perfusion were identified: choke anastomosis type (8/10) and true anastomosis type (2/10). The former formed multiple choke anastomoses near the midline. In the "super-thin flap" layer, arterial perfusion density on the ipsilateral side was significantly higher compared to that on the contralateral side. The arterioles on the ipsilateral side exhibited a dense and uninterrupted distribution, whereas those on the contralateral side appeared sparse and dispersed. The latter exhibited an alternative perfusion pattern; the bilateral arterial vessels were connected with 3 to 5 true anastomoses near the midline. Furthermore, the microscopic architecture confirmed a uniform distribution of arterioles that remained continuous from ipsilateral to contralateral sides in the "super-thin flap" layer. This study demonstrated that choke anastomosis not only impairs blood perfusion in the adjacent angiosomes but also acts as a shunt converter to impact the blood supply of distal skin flaps at different levels through the "trans-territory diversion phenomenon." This results in necrosis of the superficial dermis while preserving survival of the deep subcutaneous adipose tissue.

Exploring the transcriptomic and metabolomic profiles of adipose tissues: Insights and implications for fat grafting

BackgroundExpanding on our prior research on murine fat grafts' metabolic shift, this study delves deeper into the metabolic profiles of human adipose tissues, specifically the superficial subcutaneous adipose tissue (SSAT) and deep subcutaneous adipose tissue (DSAT). MethodsUtilizing RNA-sequencing, metabolome, and metabolic flux analyses, we examined SSAT and DSAT samples obtained during deep inferior epigastric perforator flap breast reconstructions. Transcript data underwent unsupervised hierarchical clustering and Gene set enrichment analysis. Metabolomics involved analyzing samples for cationic and anionic metabolites via Capillary Electrophoresis Time-of-Flight Mass Spectrometry (CE-TOFMS), followed by principal component analysis (PCA) and heat map generation. Additionally, primary adipocytes from SSAT and DSAT were assessed using the Seahorse® extracellular flux analyzer. ResultsPCA and heat map analyses highlighted distinct transcriptome and metabolome differences between SSAT and DSAT. SSAT predominantly upregulated genes linked to adipogenesis (false discovery rate [FDR] q < 0.0001), oxidative phosphorylation (FDR q < 0.0001), fatty acid metabolism (FDR q <0.0001), and glycolysis (FDR q = 0.001). In contrast, DSAT showed a significant upregulation in inflammatory response genes (FDR q <0.05). Metabolite analysis revealed an abundance of glycolytic metabolites in SSAT, whereas DSAT was rich in metabolites associated with fatty acid metabolism and oxidative phosphorylation. Cellular flux analysis further confirmed SSAT's elevated glycolysis and spare oxidative phosphorylation capacities. ConclusionOur results highlight the metabolic uniqueness of SSAT and DSAT in humans, with SSAT exhibiting superior metabolic flexibility. The implications of these metabolic differences, especially in fat grafting procedures, necessitate further research and exploration in future studies. Data availabilityThe ribonucleic acid sequencing data were deposited in the Gene Expression Omnibus database (GSE216803). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216803 (GEO token: qnsngiuqplqdpaf).

Evaluation of thermodynamic bioeffects of long-pulsed 1064 nm laser in the photothermal lipolysis.

To evaluate the lipolysis effect of air cooling assisted long-pulsed 1064 laser for improving local adiposity. The second-level (pulse duration of 0.3-60 s) long-pulsed Nd:YAG 1064 nm laser (LP1064 nm) with or without forced-air cooling was used to irradiate ex-vivo subcutaneous adipose tissue (SAT)of pig or human and in-vivo inguinal fat tissue of Sprague Dawley rats. The temperature of skin surface as well as 5 mm deep SAT was monitored by a plug-in probe thermal couple, and the former was confined to 39°C or 42°C during the treatment. Histological analysis of SAT response was evaluated by SAT sections stained with hematoxylin-eosin and oil red O. Ultra-microstructure changes were examined by transmission electron microscopy. A pilot study on human subject utilizing LP1064 nm laser with air cooling was conducted. The changes in gross abdomen circumference and ultrasonic imaging were studied. Histological examination showed that LP1064 nm laser treatment induced adipocyte injury and hyperthermic lipolysis both in- and ex-vivo. It was also confirmed by clinical practice on patients. By real-time temperature monitoring, we found that in comparison with LP1064 nm laser alone, additional air cooling could increase the temperature difference between epidermis and SAT, promoting heat accumulation deep in fat tissue, as well as providing better protection for epidermis. LP1064 nm laser provided reliable adipose tissue thermolysis when the temperature of skin surface was sustained at 39°C or 42°C for 10 min. Application of air-cooling during the laser treatment achieved better effect and safety of photothermal lipolysis. LP1064 nm laser, as a noninvasive device, has comparable thermal lipolysis effect as other common heat-generating devices.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI

BackgroundExisting literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PurposeTo implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. Material and methodsMRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). ResultsThe proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. ConclusionConvolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

FRI488 The Effect Of Thyroid Stimulating Hormone On Brown Adipose Tissue In Humans

Abstract Disclosure: L. Salej: None. S.D. Kodani: None. N. Chaves: None. K.N. Youssef: None. R. Monahan-Earley: None. H. Halle: None. H. Shaelah: None. P. Annie: None. J.A. Parker: None. A.M. Cypess: None. G. Kolodny: None. Y. Tseng: None. B.C. James: None. A. Gavrila-Filip: None. Obesity and diabetes are two main public health concerns due to their high impact on global morbidity and mortality. In an effort to find new treatment strategies, highly active metabolic tissues such as brown adipose tissue (BAT) have been studied as potential targets. Animal studies have shown that TSH may have a direct local effect on BAT mass and activity by stimulating local T3 production via increased deiodinase-2 (DIO2) expression and also by increasing the expression of uncoupling protein-1 (UCP-1), the key molecule in BAT thermogenesis. We hypothesized that high circulating TSH levels could increase BAT activity by increasing local T3 production and generating a local tissue "thyrotoxicosis". We studied 7 patients with thyroid cancer who underwent thyroid surgery and required recombinant TSH (rhTSH) administration for standard follow-up procedures. Each patient underwent 2 PET-CT scans for assessment of BAT volume and activity, first one day after the rhTSH administration (high TSH state) and then 1-3 months later on suppressive thyroid hormone (TH) treatment (low TSH state). Indirect calorimetry and serum thyroid function tests, fasting glucose, insulin, HbA1c, and lipid panel were measured. Our results show that there was a statistically significant difference in TSH levels (p = 0.0095), with stable circulating T4 and T3 between the low and high TSH states. There was no statistically significant difference in the BAT volume and activity (SUVmax) between the high TSH and low TSH states. Age was a significant predictor of BAT SUVmax (p = 0.008; coeff = -0.39, CI = -0.65-0.13), while BMI was a significant predictor for resting energy expenditure (REE) (p = 0.04; coeff = -203.95, CI = -396.12 - -10.78). Based on these findings, along with those from our previous study[1] showing that circulating TH levels may not be directly correlated with BAT function, we have extended our study to assess the intracellular thyroid hormone status in BAT. We have collected deep peri-thyroidal adipose tissue and subcutaneous white adipose tissue (WAT) as a control group from patients undergoing thyroid surgery. In these samples, we will measure mRNA expression of TSH receptors, TH receptors, β-adrenergic receptors, DIO2 and UCP-1 and evaluate for correlations with circulating TSH and TH levels as well as different metabolic parameters to get a deeper insight into BAT function in humans. Reference: 1. Gavrila A et al. Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status. Thyroid. 2017 Jan 1;27(1):1-10. Presentation: Friday, June 16, 2023

DNA Methylation at ABCG1 and Long-term Changes in Adiposity and Fat Distribution in Response to Dietary Interventions: The POUNDS Lost Trial.

To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight loss interventions with long-term changes in adiposity and body fat distribution. The current study included overweight/obese participants from the POUNDS Lost trial. Blood levels of regional DNA methylation at ABCG1 were profiled by high-resolution methylC-capture sequencing at baseline among 673 participants, of whom 598 were followed up at 6 months and 543 at 2 years. Two-year changes in adiposity and computed tomography-measured body fat distribution were calculated. Regional DNA methylation at ABCG1 showed significantly different associations with long-term changes in body weight and waist circumference at 6 months and 2 years in dietary interventions varying in protein intake (interaction P < 0.05 for all). Among participants assigned to an average-protein (15%) diet, lower baseline regional DNA methylation at ABCG1 was associated with greater reductions in body weight and waist circumference at 6 months and 2 years, whereas opposite associations were found among those assigned to a high-protein (25%) diet. Similar interaction patterns were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (interaction P < 0.05 for all). Baseline DNA methylation at ABCG1 interacted with dietary protein intake on long-term decreases in adiposity and body fat distribution. Participants with lower methylation at ABCG1 benefitted more in long-term reductions in body weight, waist circumference, and body fat distribution when consuming an average-protein diet.

Comparison of therapeutic effects of mesenchymal stem cells derived from superficial and deep subcutaneous adipose tissues

BackgroundFibrosis is a common histological feature in the process from chronic organ injury to organ failure. Chronic tissue injury causes inflammatory cell infiltration into the injured tissue. The persistence of this inflammatory cell infiltration leads to fibrosis and organ failure. Adipose-derived mesenchymal stem cells (ASCs) have received much attention as a regenerative therapeutic tool to prevent progression from organ injury to failure. Subcutaneous abdominal adipose tissue is divided into superficial and deep layers by a superficial fascia. Adipose tissue easily collected by liposuction is usually obtained from a deep layer, so ASCs derived from a deep layer are generally used for regenerative medicine. However, no research has been conducted to investigate differences in the therapeutic effects of ASCs from the superficial and deep layers (Sup-ASCs and Deep-ASCs, respectively). Therefore, we compared the therapeutic potencies of Sup-ASCs and Deep-ASCs.MethodsASCs were isolated from superficial and deep subcutaneous abdominal adipose tissues collected from patients who underwent breast reconstruction. We first compared cell characteristics, such as morphology, cell proliferation, cell surface markers, adipogenic and osteogenic differentiation, cell senescence markers, and expression of coagulation and anticoagulant factors between Sup-ASCs and Deep-ASCs. Furthermore, we compared their ability to promote polarization of M2 macrophages and to inhibit transforming growth factor (TGF)-β/Smad signaling using THP-1 cells and TGF-β1 stimulated HK-2 cells incubated with conditioned media from Sup-ASCs or Deep-ASCs. In in vivo experiments, after renal ischemia–reperfusion injury (IRI) procedure, Sup-ASCs or Deep-ASCs were injected through the abdominal aorta. At 21 days post-injection, the rats were sacrificed and their left kidneys were collected to evaluate fibrosis. Finally, we performed RNA-sequencing analysis of Sup-ASCs and Deep-ASCs.ResultsSup-ASCs had greater proliferation and adipogenic differentiation compared with Deep-ASCs, whereas both ASC types had similar morphology, cell surface markers, senescence markers, and expression of coagulation and anticoagulant factors. Conditioned media from Sup-ASCs and Deep-ASCs equally promoted polarization of M2 macrophages and suppressed TGF-β/Smad signaling. Moreover, administration of Sup-ASCs and Deep-ASCs equally ameliorated renal fibrosis induced by IRI in rats. RNA-sequencing analysis revealed no significant difference in the expression of genes involved in anti-inflammatory and anti-fibrotic effects between Sup-ASCs and Deep-ASCs.ConclusionsThese results indicate that both Sup-ASCs and Deep-ASCs can be used effectively and safely as an intravascular ASC therapy for organ injury.

The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity.

Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention. In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age. To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months' attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age. Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging. The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai).

Abstract 65: DNA Methylation at ABCG1 and Long-Term Changes in Adiposity in Response to Diet Interventions: The POUNDS Lost Trial

Introduction: Epigenome-wide association studies identified that DNA methylation (DNAm) at the ABCG1 gene (cg06500161) was associated with obesity. However, little is known about whether DNAm at ABCG1 is associated with long-term changes in adiposity and body fat distribution in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying DNAm at ABCG1 might respond differently to dietary weight-loss interventions on long-term changes in adiposity and body fat distribution. Methods: The current study included 673 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm level was profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at ABCG1 was defined as the average methylation level over CpGs within ± 250 bp of cg06500161. Two-year changes in adiposity and Computed Tomography (CT)-measured body fat distribution were calculated. Results: We found that regional DNAm at ABCG1 significantly interacted with dietary protein intake on long-term changes in body weight and waist circumference (WC) at 6 months and 2 years (P-interaction&lt;0.05 for all, Figure ). Among participants assigned to an average-protein (15%) diet, lower regional DNAm at ABCG1 was associated with greater reductions in body weight and WC at 6 months and 2 years, while opposite associations were found among those assigned to a high-protein (25%) diet. Similar interactions were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (P-interaction&lt;0.05 for all). Conclusion: Our data indicate that DNAm at ABCG1 interacted with dietary protein intake on long-term changes in adiposity and body fat distribution. Participants with hypomethylation at ABCG1 benefited more in long-term improvement in adiposity and body fat distribution by consuming an average-protein diet.

From the Editor’s Desk...

From the Editor’s Desk...

Total Polyunsaturated Fatty Acid Level in Abdominal Adipose Tissue as an Independent Predictor of Recurrence-Free Survival in Women with Ovarian Cancer.

Prognostic factors for epithelial ovarian cancers (EOCs) are in particular clinical factors such as pathology staging at diagnosis (FIGO stages), genetic mutation, or histological phenotypes. In the present study, FIGO stage, tumor residue after surgery, and body mass index were clinical predictors of recurrence-free survival (RFS). Nonetheless, a number of studies support a lipid metabolism disorder in ovarian cancer patients. The objective of this pilot study was to explore whether fatty acid composition of adipose reflecting the qualitative dietary intake and fatty acids metabolism may be associated with RFS. Forty-six women with EOCs and six with borderline ovarian tumors between March 2017 and January 2020 were included in this prospective study at Tours university teaching hospital (central France). The patients involved in the present study are part of the METERMUS trial (clinicaltrials.gov NCT03027479). Adipose tissue specimens from four abdominal locations (superficial and deep subcutaneous, visceral (pericolic), and omental) were collected during surgery or exploratory laparoscopy. A fatty acid profile of adipose tissue triglycerides was established by gas chromatography. Fatty acids composition was compared among the four locations using nonparametric Friedman's ANOVA test for repeated measures. Median follow-up of EOC patients was 15 months and patients' RFS was analyzed using Kaplan-Meier survival curves and log-rank test by separating patients into two groups according to median fatty acid levels. The content of long-chain saturated fatty acids (SFAs) was increased and that of long-chain polyunsaturated fatty acids (PUFAs) decreased in deep versus superficial subcutaneous adipose tissue in EOC patients. Nevertheless, the content of total SFAs was ~28%, monounsaturated fatty acids (MUFAs) ~55%, PUFAs n-6 ~11.5%, and PUFAs n-3 about 1.3%, whatever the adipose tissue. When EOC patients were separated into two groups by median fatty acid content, total PUFAs (n-6+n-3) levels, whatever the adipose tissue, were positively and independently associated with RFS. RFS was about two times longer in EOC patients with high versus low total PUFA content (median survival: 12 vs. 27 months, p = 0.01 to &lt;0.0001 according to the tissue). Content of total PUFAs (n-6+n-3) in abdominal adipose tissue (visceral and subcutaneous) are new prognostic factors in EOC.

Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement. Adult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n= 76). Adipose tissue compartment volumes were obtained using MRI. Treatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p= 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p= 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient= -2.001 and -0.083, p= 0.044 and 0.033, respectively). In adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF. NCT01265498. Although central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

Exploring the relationship of brown adipose tissue to bone microarchitecture using 7T MRI and micro-CT.

Brown adipose tissue (BAT) is involved both in energy production and bone metabolism. The purpose of this study was to analyze the relationship between BAT and microarchitecture at cancellous and cortical bone using Kunming mice and the methods of 7T magnetic resonance imaging (MRI) combined with micro-CT. Twenty-four female Kunming mice were examined by 7T MRI and measured T2* relaxation time on the deep and superficial interscapular BAT (iBAT) and subcutaneous white adipose tissue (sWAT). Cancellous bone microarchitecture of the distal femur and cortical bone of the middle femur were examined by micro-CT. A paired t-test was used to analyze the differences in T2* values between iBAT and sWAT. The correlation between BAT T2* values and bone microstructure parameters were analyzed using Pearson's correlation. T2* values of the deep and superficial iBAT (6.36±3.31 ms and 6.23±2.61 ms) were significantly shorter than those of sWAT (16.30±3.05 ms, t(deep) iBAT=-10.816), t(superficial) iBAT =-12.276, p<0.01). Deep iBAT T2* values were significantly and negatively correlated with bone volume, cancellous thickness, and bone thickness (Th) and trabecular thickness (Tb.Th) of the cancellous bone of femur. Deep iBAT T2* values were significantly and positively correlated with the structural model index of cancellous bone of femur. Deep iBAT T2* values were significantly and negatively correlated with bone mineral density of the cortical bone of femur. MRI can distinguish the two adipose tissues from each other. T2* values of BAT were lower than WAT on MRI. BAT related bone remodeling was more correlated with the microstructure of cancellous bone than that of cortical bone.

Changes in circulating microRNAs-99/100 and reductions of visceral and ectopic fat depots in response to lifestyle interventions: the CENTRAL trial

MicroRNAs (miRNAs) are short noncoding RNAs and important posttranscriptional regulators of gene expression. Adipose tissue is a major source of circulating miRNAs; adipose-related circulating miRNAs may regulate body fat distribution and glucose metabolism. We investigated how changes in adipose-related circulating microRNAs-99/100 (miR-99/100) in response to lifestyle interventions were associated with improved body fat distribution and reductions of diabetogenic ectopic fat depots among adults with abdominal obesity. This study included adults with abdominal obesity from an 18-mo diet and physical activity intervention trial. Circulating miR-99a-5p, miR-99b-5p, and miR-100-5p were measured at baseline and 18 mo; changes in these miRNAs in response to the interventions were evaluated. The primary outcomes were changes in abdominal adipose tissue [visceral (VAT), deep subcutaneous (DSAT), and superficial subcutaneous (SSAT) adipose tissue; cm2] (n=144). The secondary outcomes were changes in ectopic fat accumulation in the liver (n=141) and pancreas (n=143). Greater decreases in miR-100-5p were associated with more reductions of VAT (β±SE per 1-SD decrease: -9.63±3.13 cm2; P=0.0025), DSAT (β±SE: -5.48±2.36 cm2; P=0.0218), SSAT (β±SE: -4.64±1.68 cm2; P=0.0067), and intrahepatic fat percentage (β±SE: -1.54%±0.49%; P=0.0023) after the interventions. Similarly, participants with greater decrease in miR-99a-5p had larger 18-mo reductions of VAT (β±SE: -10.12±3.31 cm2 per 1-SD decrease; P=0.0027) and intrahepatic fat percentage (β±SE: -1.28%±0.52%; P=0.015). Further, decreases in circulating miR-99b-5p (β±SE: per 1-SD decrease: -0.44%±0.21%; P=0.038) and miR-100-5p (β±SE: -0.50%±0.23%; P=0.033) were associated with a decrease in pancreatic fat percentage, as well as improved glucose metabolism and insulin secretion at 18 mo. Decreases in circulating miR-99-5p/100-5p expression induced by lifestyle interventions were related to improved body fat distribution and ectopic fat accumulation. Our study suggests that changes in circulating adipose-related miR-99-5p/100-5p may be linked to reducing diabetogenic fat depots in patients with abdominal obesity.This trial was registered at clinicaltrials.gov as NCT01530724.

The Kynurenine Pathway Metabolites in Cord Blood Positively Correlate With Early Childhood Adiposity.

ContextThe kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth.ObjectiveIn this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years.MethodsLiquid chromatography–tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age.ResultsCord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years.ConclusionSeveral cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity.

Determinants of cord blood adipokines and association with neonatal abdominal adipose tissue distribution

BackgroundCord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother–offspring cohort.MethodsGrowing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother–offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed.ResultsIndian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only.ConclusionsCord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.

Comparison between handheld ultrasound and regional and whole-body dual energy x-ray absorptiometry (DXA) for body fat assessment.

To determine the extent of agreement between a handheld ultrasound (US) attached to an android tablet and the reference method dual energy x-ray absorptiometry (DXA) for the measurement of adiposity. A whole-body DXA scan and abdominal adipose tissue thickness measurements using a handheld US were obtained from 104 adults (63 females, 41 males). Body fat percent (BF%), total fat mass (kg), and trunk fat mass (kg) were obtained from DXA. Subcutaneous adipose tissue (SAT), superficial subcutaneous adipose tissue (SSAT), and deep subcutaneous adipose tissue (DSAT) thickness were obtained from US. Sex-specific total fat mass, trunk fat mass, and BF% estimates by US were compared with DXA. Spearman's correlations and Bland-Altman plots were used to assess agreement between the methods. US SAT correlated strongly with total fat mass for both females (rs=0.74) and males (rs=0.87) as did trunk fat mass (females, rs=0.81; males, rs=0.83); as did SSAT and DSAT (females: rs=0.65 and rs=0.66; males: rs=0.63 and rs=0.85, respectively, all p-values < 0.0001). Bland-Altman plots demonstrated strong agreement for total and trunk fat mass for both males and females. For BF%, acceptable limits of agreement were observed for males but not for females, substantial proportional bias as indicated by a negative slope was noted for BF% using SAT (r=-0.298, p=0.0177). The handheld US and technique to analyze abdominal adipose tissue thickness showed strong agreement with DXA results and generated highly comparable estimates for total and trunk fat mass for both sexes.

Cutaneous metastatic osteosarcoma – A rare case report

Abstract Introduction/Objective Osteosarcoma is an aggressive malignant primary bone tumor with common metastases to lungs via hematogenous spread. Other common sites of metastasis include bone and kidneys. Metastasis (excluding extraskeletal) to the skin is extremely rare. To date, roughly 12 cases of cutaneous metastasis have been reported in the literature. Methods/Case Report We report a 44-year-old female patient with a history of osteosarcoma of proximal tibia who underwent wide local excision in 2018 and subsequent chemotherapy. Approximately 2 years after her initial diagnosis, she presented with a painful mass in the left mid-thigh. Imaging studies revealed a 1.7 cm calcified nodule suspicious for metastatic osteosarcoma or a partially calcified granuloma. Fat necrosis and old hematoma were also considered in the radiographic differential, although less likely. An excisional biopsy was performed, which showed a high grade osteoid-producing tumor involving the deep dermis and subcutaneous adipose tissue confirming a metastasis of osteosarcoma. A new skin nodule developed at the same site six months later; though radiographic imaging studies were suggestive of subcutaneous fat stranding in the setting of cellulitis or vascular insufficiency. Given her prior history, another excisional biopsy was performed, which showed recurrent metastatic osteosarcoma. Results (if a Case Study enter NA) NA Conclusion Metastatic osteosarcoma to the skin is a rarely reported event in the literature. The prior clinical history and high index of clinical suspicion are essential in rendering the correct diagnosis. As the skin may be the first site of metastases it is important to include metastatic osteosarcoma in the differential in patients with a prior history of osteosarcoma who develops new skin or subcutaneous lesions. This case highlights the importance of providing history to the pathologist, as other tumors and non-neoplastic lesions can mimic osteosarcoma, particularly in small biopsy specimens. The easier access to the skin/ subcutis could also aid in obtaining tissue for molecular testing.

A novel conjunctive microenvironment derived from human subcutaneous adipose tissue contributes to physiology of its superficial layer

BackgroundIn human subcutaneous adipose tissue, the superficial fascia distinguishes superficial and deep microenvironments showing extensions called retinacula cutis. The superficial subcutaneous adipose tissue has been described as hyperplastic and the deep subcutaneous adipose tissue as inflammatory. However, few studies have described stromal-vascular fraction (SVF) content and adipose-derived stromal/stem cells (ASCs) behavior derived from superficial and deep subcutaneous adipose tissue. In this study, we analyzed a third conjunctive microenvironment: the retinacula cutis superficialis derived from superficial subcutaneous adipose tissue.MethodsThe samples of abdominal human subcutaneous adipose tissue were obtained during plastic aesthetic surgery in France (Declaration DC-2008-162) and Brazil (Protocol 145/09).ResultsThe SVF content was characterized in situ by immunofluorescence and ex vivo by flow cytometry revealing a high content of pre-adipocytes rather in superficial subcutaneous adipose tissue microenvironment. Adipogenic assays revealed higher percentage of lipid accumulation area in ASCs from superficial subcutaneous adipose tissue compared with retinacula cutis superficialis (p < 0.0001) and deep subcutaneous adipose tissue (p < 0.0001). The high adipogenic potential of superficial subcutaneous adipose tissue was corroborated by an up-regulation of adipocyte fatty acid-binding protein (FABP4) compared with retinacula cutis superficialis (p < 0.0001) and deep subcutaneous adipose tissue (p < 0.0001) and of C/EBPα (CCAAT/enhancer-binding protein alpha) compared with retinacula cutis superficialis (p < 0.0001) and deep subcutaneous adipose tissue (p < 0.0001) microenvironments. Curiously, ASCs from retinacula cutis superficialis showed a higher level of adiponectin receptor gene compared with superficial subcutaneous adipose tissue (p = 0.0409), widely known as an anti-inflammatory hormone. Non-induced ASCs from retinacula cutis superficialis showed higher secretion of human vascular endothelial growth factor (VEGF), compared with superficial (p = 0.0485) and deep (p = 0.0112) subcutaneous adipose tissue and with adipogenic-induced ASCs from superficial (p = 0.0175) and deep (p = 0.0328) subcutaneous adipose tissue. Furthermore, ASCs from retinacula cutis superficialis showed higher secretion of Chemokine (C–C motif) ligand 5 (CCL5) compared with non-induced (p = 0.0029) and induced (p = 0.0089) superficial subcutaneous adipose tissue.ConclusionsThis study highlights the contribution to ASCs from retinacula cutis superficialis in their angiogenic property previously described for the whole superficial subcutaneous adipose tissue besides supporting its adipogenic potential for superficial subcutaneous adipose tissue.