Unique role for lncRNA HOTAIR in defining depot-specific gene expression patterns in human adipose-derived stem cells.

Accumulation of fat above the waist is an important risk factor in developing obesity-related comorbidities independently of BMI or total fat mass. Deciphering the gene regulatory programs of the adipose tissue precursor cells within upper body or abdominal (ABD) and lower body or gluteofemoral (GF) depots is important to understand their differential capacity for lipid accumulation, maturation, and disease risk. Previous studies identified the HOX transcript antisense intergenic RNA (HOTAIR) as a GF-specific lncRNA; however, its role in adipose tissue biology is still unclear. Using three different approaches (silencing of HOTAIR in GF human adipose-derived stem cells [GF hASCs], overexpression of HOTAIR in ABD hASCs, and ChIRP-seq) to localize HOTAIR binding in GF hASC chromatin, we found that HOTAIR binds and modulates expression, both positively and negatively, of genes involved in adipose tissue-specific pathways, including adipogenesis. We further demonstrate a direct interaction between HOTAIR and genes with high RNAPII binding in their gene bodies, especially at their 3' ends or transcription end sites. Computational analysis suggests HOTAIR binds preferentially to the 3' ends of genes containing predicted strong RNA-RNA interactions with HOTAIR. Together, these results reveal a unique function for HOTAIR in hASC depot-specific regulation of gene expression.

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice.

Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages' engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.

Effect of tirzepatide on body fat distribution pattern in people with type 2 diabetes.

AIMS: To describe the overall fat distribution patterns independent of body mass index (BMI) in participants with type 2 diabetes (T2D) in the SURPASS-3 MRI substudy by comparison with sex- and BMI-matched virtual control groups (VCGs) derived from the UK Biobank imaging study at baseline and Week 52. METHODS: For each study participant at baseline and Week 52 (N = 296), a VCG of ≥150 participants with the same sex and similar BMI was identified from the UK Biobank imaging study (N = 40 172). Average visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT) and liver fat (LF) levels and the observed standard deviations (SDs; standardized normal z-scores: z-VAT, z-aSAT and z-LF) were calculated based on the matched VCGs. Differences in z-scores between baseline and Week 52 were calculated to describe potential shifts in fat distribution pattern independent of weight change. RESULTS: Baseline fat distribution patterns were similar across pooled tirzepatide (5, 10 and 15 mg) and insulin degludec (IDeg) arms. Compared with matched VCGs, SURPASS-3 participants had higher baseline VAT (mean [SD] z-VAT +0.42 [1.23]; p < 0.001) and LF (z-LF +1.24 [0.92]; p < 0.001) but similar aSAT (z-aSAT -0.13 [1.11]; p = 0.083). Tirzepatide-treated participants had significant decreases in z-VAT (-0.18 [0.58]; p < 0.001) and z-LF (-0.54 [0.84]; p < 0.001) but increased z-aSAT (+0.11 [0.50]; p = 0.012). Participants treated with IDeg had a significant change in z-LF only (-0.46 [0.90]; p = 0.001), while no significant changes were observed for z-VAT (+0.13 [0.52]; p = 0.096) and z-aSAT (+0.09 [0.61]; p = 0.303). CONCLUSION: In this exploratory analysis, treatment with tirzepatide in people with T2D resulted in a significant reduction of z-VAT and z-LF, while z-aSAT was increased from an initially negative value, suggesting a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.

Impact of physical fitness and exercise training on subcutaneous adipose tissue beiging markers in humans with and without diabetes and a high-fat diet-fed mouse model.

AIMS: Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice. MATERIALS AND METHODS: Gene expression levels of established beiging markers were measured in scWAT biopsies of humans with (n = 28) or without type 2 diabetes (n = 28), stratified by spiroergometry into low (L-FIT; n = 14 each) and high physical fitness (H-FIT; n = 14 each). High-fat diet-fed FVB/N mice underwent voluntary wheel running, treadmill training or no training (n = 8 each group). Following the training intervention, mitochondrial respiration and content of scWAT were assessed by high-resolution respirometry and citrate synthase activity, respectively. RESULTS: Secreted CD137 antigen (Tnfrsf9/Cd137) expression was three-fold higher in glucose-tolerant H-FIT than in L-FIT, but not different between H-FIT and L-FIT with type 2 diabetes. In mice, both training modalities increased Cd137 expression and enhanced mitochondrial content without changing respiration in scWAT. Treadmill but not voluntary wheel running led to improved whole-body insulin sensitivity. CONCLUSIONS: Higher physical fitness and different exercise interventions associated with higher gene expression levels of the beiging marker CD137 in healthy humans and mice on a high-fat diet. Humans with recent-onset type 2 diabetes show an impaired adipose tissue-specific response to physical activity.

Automated Deep Learning-Based Segmentation of Abdominal Adipose Tissue on Dixon MRI in Adolescents: A Prospective Population-Based Study.

BACKGROUND. The prevalence of childhood obesity has increased significantly worldwide, highlighting a need for accurate noninvasive quantification of body fat distribution in children. OBJECTIVE. The purpose of this study was to develop and test an automated deep learning method for subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) segmentation using Dixon MRI acquisitions in adolescents. METHODS. This study was embedded within the Generation R Study, a prospective population-based cohort study in Rotterdam, The Netherlands. The current study included 2989 children (1432 boys, 1557 girls; mean age, 13.5 years) who underwent investigational whole-body Dixon MRI after reaching the age of 13 years during the follow-up phase of the Generation R Study. A 2D competitive dense fully convolutional neural network model (2D-CDFNet) was trained from scratch to segment abdominal SAT and VAT using Dixon MRI-based images. The model underwent training, validation, and testing in 62, eight, and 15 children, respectively, who were selected by stratified random sampling, with manual segmentations used as reference. Segmentation performance was assessed using the Dice similarity coefficient and volumetric similarity. Two observers independently performed subjective visual assessments of automated segmentations in 504 children, selected by stratified random sampling, with undersegmentation and oversegmentation scored on a scale of 0-3 (with a score of 3 denoting nearly perfect segmentation). For 2820 children for whom complete data were available, Spearman correlation coefficients were computed among MRI measurements and BMI and dual-energy x-ray absorptiometry (DEXA)-based measurements. The model used (gitlab.com/radiology/msk/genr/abdomen/cdfnet) is publicly available. RESULTS. In the test dataset, the mean Dice similarity coefficient and mean volu-metric similarity, respectively, were 0.94 ± 0.03 [SD] and 0.98 ± 0.01 [SD] for SAT and 0.85 ± 0.05 and 0.92 ± 0.04 for VAT. The two observers assigned a score of 3 for SAT in 94% and 93% for the undersegmentation proportion and in 99% and 99% for the oversegmentation proportion, and they assigned a score of 3 for VAT in 99% and 99% for the undersegmentation proportion and in 95% and 97% for the oversegmentation proportion. Correlations with SAT and VAT were 0.808 and 0.698 for BMI and 0.941 and 0.801 for DEXA-derived fat mass. CONCLUSION. We trained and evaluated the 2D-CDFNet model on Dixon MRI in adolescents. Quantitative and qualitative measures of automated SAT and VAT segmentations indicated strong model performance. CLINICAL IMPACT. The automated model may facilitate large-scale studies investigating abdominal fat distribution on MRI among adolescents as well as associations of fat distribution with clinical outcomes.

Relationship between muscle and subcutaneous adipose tissue size and density and proximal femur bone in elderly women with hip fracture.

BACKGROUND: Both osteoporosis and sarcopenia are associated with aging, increasing the likelihood of falls in older adults and consequently raising the risk of hip fractures (HF). AIMS: To explore the relationship between the size and density of muscle and subcutaneous adipose tissue (SAT) and the bone mineral density (BMD) of the proximal femur in elderly women with HF. METHODS: Quantitative computed tomography (QCT) was conducted on the hips of 661 female participants who experienced low-energy acute HFs to measure both areal BMD (aBMD) and volume BMD (vBMD). Measurements were taken for the cross-sectional area (CSA) and density of the muscle around the hip and adjacent SAT. Multivariable linear regression models were applied to assess the relationship between these parameters. RESULTS: Most increases in the density of the gluteus medius and minimus muscle (G.Med/MinM) were correlated with higher BMD in the femoral neck fracture (FNF) group with osteoporosis. In the FNF group, gluteus maximus muscle (G.MaxM) density was negatively associated with the BMD parameters of the proximal femur in individuals with osteoporosis, while they were positively associated with nonosteoporosis. In the intertrochanteric fracture (ITF) group without osteoporosis, both FN aBMD and FN vBMD showed significant correlations with G.Med/MinM density. DISCUSSION: In women with HFs, bone and muscle are closely related. CONCLUSIONS: In older women with HFs, density but not CSA of the G.Med/MinM were associated with BMD parameters of the proximal femur. Osteoporosis may influence the relationship between G.MaxM density and proximal femur BMD in elderly women with FNF.

A new method that facilitates the diagnosis of endometrial cancer: the ratio of endometrial thickness to the full thickness of the uterine wall and subcutaneous adipose tissue measurements.

Introduction: The aim of the present study was to investigate the association between some risk factors and endometrial pathologies determined by transvaginal sonography (TVS), as well as the diagnostic predictive values of serum oestradiol (E2) levels, subcutaneous adipose tissue (SAT) thickness, endometrium thickness (ET), and the ratio of ET to uterine wall full thickness (UWT) in differential diagnosis of malignant, precancerous, and benign pathologies of endometrium in patients with postmenopausal bleeding (PMB) or with asymptomatic increased endometrial thickness. Material and methods: The study was conducted with 211 women who applied to the hospital with complaints of PMB or ET of 5 mm or more in their routine controls. Venous blood samples were taken for complete blood count and the measurement of E2 levels. Patients also underwent TVS; ET, UWT, and the ratio of ET to UWT were measured. Results: Menopausal age and body mass index averages were significantly higher in atypical hyperplasia and endometrial cancer (EC) groups. Endometrial thickness and endometrial thickness/uterine wall full thickness ratio measured by TVS were significantly higher in all precancerous pathologies and EC. Subcutaneous adipose tissue thickness was significantly higher in all precancerous pathologies and EC. Oestradiol levels were higher in the atypical hyperplasia and EC groups. Conclusions: Postmenopausal bleeding is a common symptom of EC, but in some cases this disease may occur asymptomatically. Measurement of the endometrium thickness, and the ratio of endometrium thickness/uterine wall full thickness and SAT thickness by sonography has a high predictive value for this disease.

Gene coexpression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep.

We have previously demonstrated that pre- and early postnatal malnutrition in sheep induced depot- and sex-specific changes in adipose morphological features, metabolic outcomes, and transcriptome in adulthood, with perirenal (PER) as the major target followed by subcutaneous (SUB) adipose tissue. We aimed to identify coexpressed and hub genes in SUB and PER to identify the underlying molecular mechanisms contributing to the early nutritional programming of adipose-related phenotypic outcomes. Transcriptomes of SUB and PER of male and female adult sheep with different pre- and early postnatal nutrition histories were used to construct networks of coexpressed genes likely to be functionally associated with pre- and early postnatal nutrition histories and phenotypic traits using weighted gene coexpression network analysis. The modules from PER showed enrichment of cell cycle regulation, gene expression, transmembrane transport, and metabolic processes associated with both sexes' prenatal nutrition. In SUB (only males), a module of enriched adenosine diphosphate metabolism and development correlated with prenatal nutrition. Sex-specific module enrichments were found in PER, such as chromatin modification in the male network but histone modification and mitochondria- and oxidative phosphorylation-related functions in the female network. These sex-specific modules correlated with prenatal nutrition and adipocyte size distribution patterns. Our results point to PER as a primary target of prenatal malnutrition compared to SUB, which played only a minor role. The prenatal programming of gene expression and cell cycle, potentially through epigenetic modifications, might be underlying mechanisms responsible for observed changes in PER expandability and adipocyte-size distribution patterns in adulthood in both sexes.

Unraveling adipose tissue proteomic landscapes in severe obesity: insights into metabolic complications and potential biomarkers.

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.

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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL TRIAL NUMBER: NCT01265498. IMPACT AND IMPLICATIONS: 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.

Abdominal fat and muscle distributions in different stages of colorectal cancer.

BACKGROUND: The purpose of this study is to explore the difference of abdominal fat and muscle composition, especially subcutaneous and visceral adipose tissue, in different stages of colorectal cancer (CRC). MATERIALS AND METHODS: Patients were divided into 4 groups: healthy controls (patients without colorectal polyp), polyp group (patients with colorectal polyp), cancer group (CRC patients without cachexia), and cachexia group (CRC patients with cachexia). Skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) were assessed at the third lumbar level on computed tomography images obtained within 30 days before colonoscopy or surgery. One-way ANOVA and linear regression were used to analyze the difference of abdominal fat and muscle composition in different stages of CRC. RESULTS: A total of 1513 patients were divided into healthy controls, polyp group, cancer group, and cachexia group, respectively. In the development of CRC from normal mucosa to polyp and cancer, the VAT area of the polyp group was significantly higher than that of the healthy controls both in male (156.32 ± 69.71 cm2 vs. 141.97 ± 79.40 cm2, P = 0.014) and female patients (108.69 ± 53.95 cm2 vs. 96.28 ± 46.70 cm2, P = 0.044). However, no significant differences were observed of SAT area between polyp group and healthy controls in both sexes. SAT area decreased significantly in the male cancer group compared with the polyp group (111.16 ± 46.98 cm2 vs. 126.40 ± 43.52 cm2, P = 0.001), while no such change was observed in female patients. When compared with healthy controls, the SM, IMAT, SAT, and VAT areas of cachexia group was significantly decreased by 9.25 cm2 (95% CI: 5.39-13.11 cm2, P < 0.001), 1.93 cm2 (95% CI: 0.54-3.32 cm2, P = 0.001), 28.84 cm2 (95% CI: 17.84-39.83 cm2, P < 0.001), and 31.31 cm2 (95% CI: 18.12-44.51 cm2, P < 0.001) after adjusting for age and gender. CONCLUSION: Abdominal fat and muscle composition, especially SAT and VAT, was differently distributed in different stages of CRC. It is necessary to pay attention to the different roles of subcutaneous and visceral adipose tissue in the development of CRC.

Oleic acid regulates the circadian rhythm of adipose tissue in obesity.

The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity.

Body Composition Predictors of Complicated Crohn's Disease.

BACKGROUND: High visceral adipose tissue (VAT) and creeping fat (CrF) in Crohn's disease (CD) have been widely recognized. The VAT to subcutaneous adipose tissue (SAT) ratio and sarcopenia have been associated with CD complications. Studies regarding the influence of body composition predictors on CD complications assessed with magnetic resonance enterography (MRE) are scarce. AIM: The aim of this study was to assess body composition parameters and CrF in opportunistic MRE as predictors of complicated CD. METHODS: This was a retrospective study of 114 patients with inflammatory (n = 54) and complicated (n = 60) CD. The semiautomated assessment of body composition and the qualitative evaluation of CrF were performed. RESULTS: Body composition parameters did not differ between both groups regarding the body mass index (p = 0.50), total adipose tissue index (TATI) (p = 0.14), subcutaneous adipose tissue index (SATI) (p = 0.17), visceral adipose tissue index (VATI) (p = 0.33), VAT/SAT ratio (p = 0.77), intramuscular adipose tissue (p = 0.64), skeletal muscle index (p = 0.22), and sarcopenia (p = 0.50). 47 strictures, 18 fistulae, and seven abscesses were identified. Fistulae were more likely to occur in patients with CrF (odds ratio [OR] 5.07, 95% confidence interval [CI] 1.76-14.56; p=<0.001) and high VAT/SAT ratio (OR: 3.82, 95% CI 1.34-10.85; p = 0.01). CONCLUSION: Body composition measurements in CD patients displayed no statistically significant difference between the groups of inflammatory and complicated disease. Nonetheless, CD patients stratified in the group of high VAT/SAT ratio and the presence of CrF should be recognized as risk groups for the occurrence of fistulae.

Inflammation biomarkers and inflammatory genes expression in metabolically healthy obese patients.

BACKGROUND AND AIMS: Obesity without metabolic alterations (Metabolically Healthy Obesity, MHO) is a condition with a risk of death and cardiovascular disease lower than that of obesity associated with metabolic alterations (Metabolically Unhealthy Obesity, MUO) and similar to that of healthy non obese individuals. Inflammation is considered as a key risk factor mediating the adverse health outcomes in obesity. METHODS AND RESULTS: We compared circulating levels of thirteen major cytokines and adipokines and the expression profiles of fifteen pro-inflammatory and two anti-inflammatory genes in visceral and subcutaneous adipose tissue in a series of 16 MHO patients and in 32 MUO patients that underwent bariatric surgery. MHO was defined according to the most applied definition in current literature. Serum levels of a large set of major cytokines and adipokines did not differ between MHO and MUO patients (p ≥ 0.15). Analyses of the expression profile of pro-inflammatory and anti-inflammatory genes in subcutaneous and visceral adipose tissue failed to show differences between MHO and MUO patients (p ≥ 0.07). Sensitivity analyses applying two additional definitions of MHO confirmed the results of the primary analysis. CONCLUSION: In a series of metabolically healthy obese patients neither circulating levels of major cytokines and adipokines nor the gene expression profile of a large set of pro-inflammatory and anti-inflammatory genes in subcutaneous and visceral fat differed from those in metabolically unhealthy obese patients.

Gender-specific associations between abdominal adipose mass and bone mineral density in the middle-aged US population.

OBJECTIVES: The relationship between abdominal adipose tissue and osteoporosis is poorly understood. The purpose of this study was to examine the associations of abdominal adipose tissue with bone mineral density (BMD) among a nationally representative sample of US middle-aged adults. MATERIAL AND METHODS: This study included 1498 participants from the National Health and Nutrition Examination Survey 2013-2014 and 2017-2018. Dual-energy x-ray absorptiometry was used to measure BMD at the lumbar spine and femoral neck, as well as to assess abdominal adipose mass by categorizing total adipose tissue (TAT) into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Linear regression was used to assess the relationship between abdominal adipose tissue and BMD, and logistic regression and generalized additive model were used to assess the associations of abdominal adipose tissue with the development of low BMD. RESULTS: In our study, men accounted for 51.3%, and the mean age and body mass index for men and women were 49.3 and 49.6 years, and 23.9 and 28.3 kg/m2, respectively. In the univariate model, we found that abdominal adipose mass was positively associated with BMD at femoral neck and spine in both genders. In the multivariate model, among men, a negative correlation was observed between TAT and SAT and BMD at the femoral neck. Additionally, higher masses of TAT, SAT, and VAT were found to significantly increase the risk of low BMD at both the femoral neck and lumbar spine. In contrast, there was no significant association between abdominal adipose mass and BMD in middle-aged women, regardless of menopausal status. CONCLUSIONS: Our finding suggested that abdominal adipose tissue, regardless of its location (SAT or VAT), may have a negative impact on BMD in middle-aged men independently of body weight, but this relationship was not observed in women. Further research is needed to confirm these findings and investigate potential mechanisms underlying these associations.

Evaluation of the relationship between abdominal fat distribution and osteoporotic vertebral compression fracture with MRI.

OBJECTIVE: This study was carried out to investigate the effects of abdominal subcutaneous adiposity and visceral adiposity on osteoporotic compression fractures. MATERIAL AND METHODS: The study group consisted of a total of 152 individuals aged 50-80 years; 76 were included in the vertebral fracture group and 76 in the healthy control group, whose bone mineral density was calculated. In order to determine the distribution of abdominal fat in both groups, four different measurements, i.e., sagittal abdominal diameter (SAD), abdominal diameter (AD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST), were made using lumbar magnetic resonance imaging (MRI). The visceral fat ratio (VFR) was also calculated based on these measurements. RESULTS: There was a significant difference between the patient and control groups in VST and DST values, both when gender distribution was and was not taken into account (p < 0.006 for all cases). There was no significant difference between the patient and control groups in SAD and AS values, both when only female patients were considered, and gender distribution was not taken into account (p > 0.25 for all cases). On the other hand, in the analysis, when only male patients were considered, the SAD and AD values of the patient group were found to be significantly lower than those of the control group (p = 0.046 and p = 0.048, respectively). CONCLUSION: In conclusion, the study findings indicated that high SAD values in the male gender and high VST and DST values in both genders were associated with low lumbar vertebral fracture risk.

Reevaluation of the topographical anatomy of the mid-thigh: A magnetic resonance and ultrasound imaging study.

Adductor canal (AC) and sciatic nerve (SN) blockades are commonly used during total knee arthroplasties for postoperative pain control. Medical professionals have begun to utilize single injection combined regional anesthesia methods due to increased patient comfort. In this study, we examined the topographical anatomy of the mid-thigh, which is recommended as the appropriate intervention level for combined AC and SN blockades, in order to provide a safe approach for clinicians. We examined 184 thigh magnetic resonance images (MRI) from 98 patients. We measured the diameter of the mid-thigh, anterior thigh muscle thickness, subcutaneous adipose tissue thickness, and SN depth on the MRIs. We obtained ultrasound (US) images of the vastoadductor membranes (VAM) of 26 volunteers, and measured the vertical distances between the greater trochanter and the adductor tubercle (A) and the greater trochanter and the upper edge of the VAM (B). We then proportioned B to A in order to determine in which part of the thigh the AC was located. The AC was in the distal third of the thigh, and the SN's depth was located in the third quarter of the thigh's diameter. Only the adductor magnus, and no neurovascular structure, was at risk of injury between the AC and the SN. The upper edge of the VAM was 6.5 cm below the mid-thigh, therefore it is not appropriate to suggest performing an AC blockade at mid-thigh. We think that it is safe to perform a combined AC and SN blockade in a single injection in selected patients.

Type 2 Diabetes in Obesity: A Systems Biology Study on Serum and Adipose Tissue Proteomic Profiles.

Obesity is associated with metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM), further increasing an already heightened cardiovascular risk. Here, amongst obese class III bariatric surgery patients, we have investigated the effect of T2DM in serum and in two, same patient, adipose tissue (AT) depots through proteomic profile expression analyses. Serum and AT samples from subcutaneous (SAT) and visceral (VAT) fat were collected during bariatric surgery. Bead-based targeted multiplex assay systems were used to simultaneously detect and quantify multiple targets in serum samples (targeted proteomics) and analyze changes in adipokine serum composition. AT samples were assessed through an untargeted proteomics approach. Through a systems biology analysis of the proteomic data, information on the affected biological pathways was acquired. In obese class III individuals, the presence of T2DM induced a significantly higher systemic release of ghrelin, GLP-1, glucagon, MMP3, BAFF, chitinase 3-like 1, TNF-R1 and TNF-R2, and a lower systemic release of IL-8. SAT and VAT proteomes belonging to the same patient showed significant differences in local protein content. While the proteins upregulated in VAT were indicative of metabolic dysregulation, SAT protein upregulation suggested adequate endocrine regulation. The presence of T2DM significantly affected VAT protein composition through the upregulation of dysregulating metabolic pathways, but SAT protein composition was not significantly modified. Our results show that T2DM induces metabolic dysregulation in obese individuals with changes in systemic marker levels and impairment of proteostasis in VAT but not in SAT.

Tissue and Circulating MicroRNAs 378 and 142 as Biomarkers of Obesity and Its Treatment Response.

Promising approaches to the treatment of obesity include increasing energy expenditure and slowing down fibrogenesis of adipose tissue. The neurotransmitter reuptake inhibitor sibutramine affects appetite and activates lipolysis in a catecholaminergic way. MicroRNAs (miRs) are considered as biomarkers of molecular genetic mechanisms underlying various processes. The profile of a number of miRs is altered in obesity, both in the circulation and in adipose tissue. The aim of this study was to assess the expression levels of miRs (hsa-miR-378a-3p, hsa-miR-142-3p) by real-time polymerase chain reaction in subcutaneous adipose tissue (SAT) and in plasma in patients with different degrees and duration of obesity and during sibutramine therapy. This study included 51 obese patients and 10 healthy subjects with normal weight who formed a control group. The study found that, before treatment, obese patients had no significant difference in the expression level of miR-378 in SAT and plasma compared to the control group, while the expression of miR-142 was significantly decreased in SAT and increased in plasma. A significant elevation in miR-378 expression level was noted in patients with first-degree obesity and duration of less than 10 years, and the decline in miR-142 increased with the duration of obesity. These data indicate a maximal increase in the expression of the adipogenesis inducer miR-378 in the early stages of obesity, a progressive decrease in the expression of the fibrogenesis inhibitor miR-142 in SAT with growth of duration of obesity and the likely presence of antifibrogenic effects of sibutramine realized through miR-142 activation.

A Network Comprised of miR-15b and miR-29a Is Involved in Vascular Endothelial Growth Factor Pathway Regulation in Thymus Adipose Tissue from Elderly Ischemic Cardiomyopathy Subjects.

As the human thymus ages, it undergoes a transformation into adipose tissue known as TAT. Interestingly, in previous research, we observed elevated levels of vascular endothelial growth factor A (VEGFA) in TAT from patients with ischemic cardiomyopathy (IC), particularly in those over 70 years old. Moreover, in contrast to subcutaneous adipose tissue (SAT), TAT in elderly individuals exhibits enhanced angiogenic properties and the ability to stimulate tube formation. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery. MicroRNAs (miRNAs) have emerged as attractive therapeutic targets, especially those that regulate angiogenic processes. The study's purpose is to determine the miRNA network associated with both the VEGFA pathway regulation and the enrichment of age-linked angiogenesis in the TAT. RT-PCR was used to analyze angiogenic miRNAs and the expression levels of their predicted target genes in both TAT and SAT from elderly and middle-aged patients treated with coronary artery bypass graft surgery. miRTargetLink Human was used to search for miRNAs and their target genes. PANTHER was used to annotate the biological processes of the predicted targets. The expression of miR-15b-5p and miR-29a-3p was significantly upregulated in the TAT of elderly compared with middle-aged patients. Interestingly, VEGFA and other angiogenic targets were significantly upregulated in the TAT of elderly patients. Specifically: JAG1, PDGFC, VEGFA, FGF2, KDR, NOTCH2, FOS, PDGFRA, PDGFRB, and RHOB were upregulated, while PIK3CG and WNT7A were downregulated. Our results provide strong evidence of a miRNA/mRNA interaction network linked with age-associated TAT angiogenic enrichment in patients with IC.