Adipose Tissue Of Patients Research Articles

Using QCT to evaluate bone mineral and abdominal adipose changes in patients with primary hyperparathyroidism and comparing it to DXA for bone status assessment: a retrospective case-control study.

BackgroundPatients with primary hyperparathyroidism (PHPT) show changes in bone metabolism and adipose tissue, but the results are inconsistent. Quantitative computed tomography (QCT) was reported useful for detecting bone mineral and adipose tissue change, but information on the role of QCT in PHPT is limited. We aimed to explore the changes of lumbar bone mineral density (BMD) and abdominal adipose tissue in patients with PHPT using QCT based on existed CT images, and to assess the consistency between QCT and dual-energy X-ray absorptiometry (DXA) in assessing bone status.MethodsThis retrospective case-control study was conducted on 48 PHPT patients, with healthy controls (HCs) matched by their age (±3 years) and gender, and the case-to-control ratio was approximately 1:3. Volumetric bone mineral density (vBMD), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) were measured by QCT in both PHPT and control groups and compared with the independent samples T-test. In the PHPT group, areal bone mineral density (aBMD) was measured by DXA. Pearson correlation analysis was used to investigate the association between QCT-derived vBMD and DXA-derived aBMD. Weighted kappa consistency analysis was used to clarify the agreement between QCT and DXA.ResultsCompared with HCs, the PHPT group had significantly lower vBMD (114.30±41.71 vs. 136.92±42.23 mg/cm3; P=0.002) and higher TAT (261.98±74.65 vs. 236.69±69.00 cm2; P=0.033); however, differences in SAT (120.81±40.19 vs. 109.94±36.83 cm2; P=0.085) and VAT (141.17±48.11 vs. 126.75±50.50 cm2; P=0.085) were not statistically significant. There was a strong correlation between QCT-derived vBMD and DXA-derived aBMD (all r>0.68; P<0.001), and a moderate consistency [kappa(w) =0.48; 95% CI: 0.29 to 0.68; P<0.001] was presented when defining bone status according to the respective diagnostic criteria.ConclusionsOur study may provide useful information regarding bone status and abdominal adipose tissue change in patients with PHPT without requiring additional scan and may further extend the clinical application value of QCT.

Conversion to Knee Arthroplasty Following Intra-Articular Injection of Microfragmented Adipose Tissue in Patients with Knee Osteoarthritis

Conversion to Knee Arthroplasty Following Intra-Articular Injection of Microfragmented Adipose Tissue in Patients with Knee Osteoarthritis

&lt;i&gt;FABP4&lt;/i&gt; gene expression in subcutaneous and visceral adipose tissue in patients with obesity and type 2 diabetes mellitus

Introduction. Obesity is associated with a high risk of developing concomitant diseases such as: metabolic syndrome, type 2 diabetes mellitus (DM2), cardiovascular pathology. FABP4 (fatty acid binding protein) is the specific lipid chaperone and an important protein for the function of adipose tissue and is one of the adipocytokines secreted by adipose tissue.The objective of the study was to investigate the FABP4 gene expression in subcutaneous and visceral adipose tissue (SAT and VAT) in patients with obesity and DM2.Methods and materials. SAT and VAT samples were obtained during bariatric surgery (N=43, BMI&gt;35): obese with DM2 (N=21), obese without DM2 (N=22). Samples for the control group without obesity (N=15, BMI&lt;30) were obtained during planned operations on the abdominal cavity. FABP4 mRNA level was estimated by real-time PCR.Results. It has been demonstrated that the mRNA level of the FABP4 gene in SAT and VAT is reduced in obesity, regardless of the manifestation of DM2 (p&lt;0.01). A negative correlation was observed between the mRNA level of the FABP4 gene in adipose tissue and the BMI index (for SAT: r=—0.327, p = 0.016; for VAT: r=—0.304, p = 0.024).Conclusion. The expression level of FABP4 gene in AT can act as a marker of AT dysfunction in obesity.

Association Between Systemic Inflamatuary Index and Epicardial Adipose Tissue in Patients with Type 2 Diabetes Mellitus

Objective: Epicardial adipose tissue is the visceral fat located between the myocardium and the pericardium. Increases in epicardial adipose tissue are closely associated with the occurrence of cardiovascular diseases. The systemic immune inflammation index is a new parameter developed to determine the inflammatory status of patients. In our study, we aimed to evaluate the relationship between systemic immun inflammation index and epicardial adipose tissue in patients with diabetes mellitus. Method: 119 patients with T2DM and 50 volunteers were included to study. SII was obtained with formulatıon of neutrophil/lymphocyte x platelet. Epicardial fat tissue was obtained by transthoracic echocardiography. The relationship between systemic immune inflammation index and epicardial adipose tissue was evaluated in patients with Diabetes Mellitus Results: In our study, ıt was shown that epicardial adipose tissue was higher in diabetic patients. There was a significant correlation between Body surface area , duration of diabetes mellitus, HbA1c, systemic immune inflammation index, mean platelet volume , neutrophil lymphocyte ratio and epicardial adipose tissue. In linear regression analysis, it was observed that duration of diabetes mellitus (β =0.049 (0.011-0.087); P=0.011) and SII (β=0.013 (0.001-0.018) P=0.008) were independent predictors of EAT. Conclusions: In our study, it was shown that there is a significant relationship between epicardial adipose tissue and systemic immune inflammation index in diabetic patients. In patients with diabetes mellitus, systemic immune inflammation index may provide a useful estimate of epicardial adipose tissue, which has been shown to be associated with cardiovascular events.

The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery

Background and aimsEpicardial and pericardial adipose tissue (EAT and PAT) associate with atherosclerosis, however, discussed to have different inflammatory properties. We examined the NLRP3 inflammasome related pathway, playing a pivotal role in atherosclerosis, in EAT, PAT and subcutaneous AT (SAT), their relationship to cell types and anthropometric measures in patients undergoing coronary artery bypass grafting. MethodsBiopsies from EAT, PAT and SAT were collected from 52 patients with coronary heart disease (CHD) (median body weight 85.0 kg) and 22 controls. RNA was extracted and expression of interleukin (IL)-1β, IL-18, NLRP3, Caspase-1, toll-like receptor 4 (TLR4), IL-6, IL-6 receptor and gp130 were analyzed by RT-PCR. ResultsLimited differences in any genes between CHD patients and controls. IL-18 and IL-6 were 4-fold higher expressed in EAT versus PAT (p < 0.01, both) and SAT (p < 0.001, both), whereas caspase-1, IL-6R and gp130 were higher expressed in SAT compared to the other compartments (all p = 0.06-<0.001). Significant correlations between SAT and PAT gene expressions (r = 0.358–0.579, all p ≤ 0.01). Especially NLRP3 and TLR4 associated with the expression of macrophages in all compartments (all p < 0.001). In EAT IL-18 correlated inversely with the expression of macrophages and T-cells. In SAT and PAT most of the mediators associated with body weight. ConclusionsHigher expression of IL-18 and IL-6 was observed in EAT in our non-obese CHD patients, not related to inflammatory cells. The NLRP3 inflammasome activation in SAT that mirrored PAT, both related to anthropometrics, suggest that SAT samples, being easily available, to a certain degree, represent adipose tissue inflammation in general.

The Quantity of Epicardial Adipose Tissue in Patients Having Ablation for Atrial Fibrillation With and Without Heart Failure

The distribution of epicardial adipose tissue (EAT) across the spectrum of heart failure (HF) has yet to be fully elucidated. The present study investigated the distribution of EAT in an HF spectrum and its association with clinical and echocardiographic parameters. A total of 326 patients who underwent contrast-enhanced computed tomography before transcatheter atrial fibrillation ablation with and without HF symptoms, and a wide range of left ventricular (LV) ejection fractions (LVEF) were included. EAT mass was quantified on contrast-enhanced computed tomography using dedicated software. A total of 36 patients had HF with reduced LVEF (HFrEF) (11.0%), 46 had HF with mid-range LVEF (HFmrEF) (14.1%), 53 had HFpEF (16.3%), and 191 did not have HF symptoms (58.6%) and were considered controls. Patients with HFpEF had the largest EAT mass, significantly higher than the control group (128 ± 36 g vs 95 ± 35 g, p <0.001), the HFmrEF group (101 ± 37 g, p <0.001), and the HFrEF group (103 ± 37 g, p=0.002). However, there were no differences in EAT mass between patients with HFrEF, HFmrEF, and controls. EAT was independently associated with E/e', LV mass index, and tricuspid regurgitation velocity. Male gender, body mass index, and C-reactive protein levels were independently associated with EAT. In conclusion, patients with HFpEF had more EAT than patients with HFmrEF, patients with HFpEF, and controls. EAT was associated with worse LV diastolic dysfunction, whereas C-reactive protein levels were independently associated with EAT, suggesting an active inflammatory component.

Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy

BackgroundThe authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.MethodsAll six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV− healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry.ResultsThe time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.ConclusionsOur findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes’ sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.

The importance of laboratory parameters of the lipid transport system and adipose tissue hormones in assessing the course of chronic.

The main manifestations of metabolic syndrome (MS) are disorders of carbohydrate and lipid metabolism and their hormonal regulation. The combined nature of metabolic disorders can significantly affect the course and prognosis of CHF in elderly people with metabolic syndrome. To determine the features of the combined effect of metabolic laboratory parameters and biological active factors of adipose tissue in patients with CHF and metabolic syndrome on the course of the disease. A comparison was made between a group of patients with CHF complicated by MS(n=37) and a group of patients with CHF without MS (n=37). The parameters of lipid metabolism (cholesterol CH and lipoproteins LP), the lipid transport system (ApoA1 and ApoB), leptin, adiponectin and resistin and their mutual relations were studied. The ratio of ApoB/ApoAI levels was indicative, which was 0.80±0.32 in patients with CHF without MS, and 1.12±0.46 in patients with CHF with MS (p <0.05). A significant correlation was found between the ratio of ApoB/ApoA1 levels and abdominal obesity (r=0.42, p<0.05), functional class of CHF (r=0.463, p<0.05), LDL-C level (r=0.518, p<0.05), and triglycerides (r=0.476, p<0.05). Also, significant results were obtained for the leptin/adiponectin ratio. For this ratio, 4 ranks were derived depending on the value of the leptin (ng/ml)/adiponectin (mcg/ml) ratio: less than 1 - rank 0 was assigned, with values of the ratio in the range 1 - 3 - rank 1, in the range 3.1 - 6 - rank 2, and above the value 6 - rank 3. Of the 22 patients who had improved CHF at the end of hospitalization, all at the beginning of hospitalization had a rank 0 or 1 ApoB/ApoA1 ratio. Thus, ranking the values of the ratio of ApoB/ApoA1 levels, and especially leptin/adiponectin, can suggest the probability of successful treatment of CHF or the probability of deterioration of the patient's condition, up to a fatal outcome.

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review.

Simple SummaryCardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is one of the most important risk factors for cardiovascular events and a promising new therapeutic target in CVDs. Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including coronary artery disease, heart failure and atrial fibrillation; compile data regarding the association between EAT’s function and the course of COVID-19; and present new potential therapeutic possibilities, aiming at modifying EAT’s function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT’s function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.

Assessment of visceral adipose tissue in patients with coronary artery disease using bioelectrical impedance analysis

Aim. To study visceral adipose tissue (VAT) content in patients with coronary artery disease (CAD) using the bioimpedance analysis, to identify metabolic disorders associated with visceral obesity, and to determine the role of individual risk factors in the formation of coronary artery lesions using modern statistical methods.Material and methods. A total of 152 patients were examined (women, 66; men, 86). The median age of patients was 63 [55;69] years. This observational study assessed anthropometric parameters, such as height, weight, body mass index, waist circumference, whole-body fat percentage, and specifically VAT mass, as well as the relationship of these parameters with blood levels of triglycerides, high-density lipoprotein cholesterol (HDL-C) and glucose. Height was measured using a metal height meter RM-1 “Diakoms”. Weight, body mass index, wholebody fat percentage, and VAT mass were measured using the Omron BF-508 body composition monitor (Omron, Japan). Epicardial adipose tissue (EAT) thickness was assessed using two-dimensional echocardiography on a Philips Sonos 5500 ultrasound system (Germany).Results. Bioimpedance analysis revealed a higher VAT content in patients with CAD compared with those without CAD (14 [11;18]% vs 13 [10;14,5]%, respectively (p=0,025)). During the ROC analysis, cut-off values for VAT ≥15% and EAT ≥7,5 mm were identified, associated with a higher risk of CAD. In multivariate analysis, only HDL-C levels were significantly associated with CAD, while at the same time, univariate analysis demonstrated the significance of VAT and EAT in predicting CAD.Conclusion. The results showed that an increased VAT content and low HDL-C level is associated with the presence of CAD.

Obesity, Adipose Tissue, and Inflammation Answered in Questions.

Background. Obesity is a global health problem of epidemic proportions, which is characterized by increased adipose tissue (AT) mass and significant repercussions in different body apparati and systems. AT is a special connective tissue, which contains several types of cells, in addition to adipocytes, and is a highly active endocrine and immune organ, which directly modulates many processes, including energy balance, metabolism, and inflammation. Summary. In this paper, the authors list and attempt to answer in a brief and simple way several questions regarding the complex relationships between obesity, adipose tissue, and inflammation, with the objective to provide an easy way to understand the main changes that occur in this pathological state. The questions are the following: Is adipose tissue only made up of adipocytes? Are adipocytes just a reservoir of free fatty acids? Do different types of fatty tissue exist? If so, which types? Can we further subcategorize the types of adipose tissue? Is it possible to form new adipocytes during adulthood? What is the role of inflammation? What is the role of macrophages? Are macrophages central mediators of obesity-induced adipose tissue inflammation and insulin resistance? What causes macrophage infiltration into adipose tissue? What is the role of hypoxia in AT alterations? Is there cross talk between adipocytes and immune cells? What other changes occur in AT in obesity? Does metabolically healthy obesity really exist? Is this a benign condition? Key messages. Obesity is a complex disease with numerous metabolic consequences, which are mainly the result of dysfunction that occurs in the adipose tissue of patients with this pathology. Understanding the pathophysiology of AT and the changes that occur in obesity would contribute to a better approach to patients with obesity, with the inherent medical implications that could result from this.

Prognostic Impact of Quality and Distribution of Adipose Tissue in Patients With Primary Central Nervous System Lymphoma.

Body composition assessment has shown promising results as a prognostic biomarker as depicted by cross-sectional imaging of several tumor entities including lymphomas. The present study sought to elucidate the prognostic relevance of subcutaneous and visceral fat tissue (SAT and VAT) in patients with primary central nervous system lymphoma (PCNSL). Overall, 74 patients (36 female patients, 46.7%) with a mean age of 64.2±12.8 years (range=23-81 years) were identified in the database with sufficient clinical and imaging data and included into this retrospective study. Fat area assessment was performed on one axial slide on L3-height derived from staging computed tomography (CT) images. Subcutaneous, visceral, and intramuscular adipose tissues (SAT, VAT, IMAT) were estimated. Also, density of SAT, VAT, and IMAT were estimated. Finally, the ratio VAT/SAT (VSR) was calculated. Overall and progression-free survival (OS and PFS) were used as study end points. In the observation period, overall, 47 patients (63.5%) died. Mean OS was 33.8±45.4 months and mean PFS was 26.6±42.7 months. The mean VAT value was 162±99.5 cm2, the mean SAT was 202.4±103.3 cm2, the mean VSR was 0.92±0.69. The hazard ratios (HRs) for overall survival were 0.87 for high VAT, 1.52 for SAT, and 0.73 for VSR in univariable analysis. For PFS it was 0.24 for VAT, 1.11 for SAT, and 1.07 for VSR. No values achieved statistical significance. Similar results were shown in Kaplan-Meier analysis for OS and PFS, respectively. Parameters of adipose tissue are not associated with OS and PFS in patients with PCNSL.

Subgroup Identification with Gene Expression Profiles of Adipose Tissue in Patients with Coronary Artery Disease.

Among many diseases, coronary artery disease (CAD) is the primary cause of mortality and morbidity worldwide. With the aim of revealing the underlying genetic characteristics of the CAD subtypes, we recruited patients with CAD and categorized them into subgroups according to the transcriptome expression profiles of the adipose tissue.With the removal of the batch effect, consensus clustering was employed to determine the subgroup numbers. Subgroup-specific genes were determined to conduct analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted gene co-expression network analysis (WGCNA) revealed the subgroup-specific WGCNA modules. Moreover, gene set enrichment analysis (GSEA) was conducted. Overrepresentation enrichment analysis (OEA) of subgroup-specific signatures was also conducted to reveal the significant gene module associated with the corresponding clinical characteristics.After the removal of the batch effect, 77 CAD objects were divided into three subgroups. It was observed that the patients in subgroup III tended to be fat. After analyzing the dominant pathways of each subgroup, we discovered that the protein digestion and absorption pathway was specifically upregulated in subgroup I, which might result from the lowest proportion of the epicardial adipose tissue (EAT) sample. Moreover, subgroup II patients had genetic characteristics of high expression of complement and coagulation cascades and TNF signaling pathway. Furthermore, Th17 cell differentiation was significantly upregulated in subgroup III, indicating that Th17 cell differentiation is related to the clinical characteristics of body mass index (BMI).In conclusion, the genetic classification of CAD subjects indicated that subjects from different subgroups may exhibit specific gene expression patterns, suggesting that more personalized treatment should be applied to patients in each subgroup.

Clinical Significance of Increased Computed Tomography Attenuation of Periaortic Adipose Tissue in Patients With Abdominal Aortic Aneurysms.

Recent imaging studies reported an association between vascular inflammation and progression of abdominal aortic aneurysm (AAA). This study investigated the clinical significance of periaortic adipose tissue inflammation derived from multidetector computed tomography angiography (MDCTA).Methods and Results:Patients with asymptomatic AAA (n=77) who underwent an index and >6 months follow-up MDCTA examinations were retrospectively investigated. MDCTA analysis included AAA diameter and the periaortic adipose tissue attenuation index (PAAI). The PAAI was defined as the mean CT attenuation value within a predefined range from -190 to -30 Hounsfield units of adipose tissue surrounding the AAA. The growth rate of the AAA was calculated as the change in diameter. AAA progression (AP) was defined as an AAA growth rate ≥5 mm/year. Univariate and multivariate logistic regression analysis were performed to determine the predictors of AP. AP was observed in 19 patients (24.7%), the median baseline AAA diameter was 38.9 mm (interquartile range [IQR] 32.7-42.9 mm), and the median growth rate was 3.1 mm/year (IQR 1.5-4.9 mm/year). Baseline AAA diameter (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.05-1.28; P=0.001) and PAAI (OR 1.12; 95% CI 1.05-1.20; P=0.004) were independent predictors of AP. PAAI was an independent and significant predictor of AP, supporting the notion that local adipose tissue inflammation may contribute to aortic remodeling.

Opposing Immune-Metabolic Signature in Visceral Versus Subcutaneous Adipose Tissue in Patients with Adenocarcinoma of the Oesophagus and the Oesophagogastric Junction.

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of adipose tissue may provide insight for this observation. We hypothesised that different metabolic pathways predominate in visceral (VAT) and subcutaneous adipose tissue (SAT) and inflammatory secretions will differ between the fat depots. Real-time ex vivo metabolic profiles of VAT and SAT from 12 OAC patients were analysed. These samples were screened for the secretion of 54 inflammatory mediators, and data were correlated with patient body composition. Oxidative phosphorylation (OXPHOS) was significantly higher in VAT when compared to SAT. OXPHOS was significantly higher in the SAT of patients receiving neoadjuvant treatment. VEGF-A, VEGF-C, P1GF, Flt-1, bFGF, IL-15, IL-16, IL-17A, CRP, SAA, ICAM-1, VCAM-1, IL-2, IL-13, IFN-γ, and MIP-1β secretions were significantly higher from VAT than SAT. Higher levels of bFGF, Eotaxin-3, and TNF-α were secreted from the VAT of obese patients, while higher levels of IL-23 and TARC were secreted from the SAT of obese patients. The angiogenic factors, bFGF and VEGF-C, correlated with visceral fat area. Levels of OXPHOS are higher in VAT than SAT. Angiogenic, vascular injury and inflammatory cytokines are elevated in VAT versus SAT, indicating that VAT may promote inflammation, linked to regulating treatment response.

A Sarcopenia-Based Prediction Model for Postoperative Complications of ex vivo Liver Resection and Autotransplantation to Treat End-Stage Hepatic Alveolar Echinococcosis.

BackgroundSarcopenia and visceral adiposity have been shown to be associated with postoperative complications in numerous diseases. However, their effects on the postoperative complications of end-stage hepatic alveolar echinococcosis (HAE) patients undergoing ex vivo liver resection and autotransplantation (ELRA) remain unclear.MethodsThis retrospective study included 101 end-stage HAE patients who underwent ELRA from January 2014 to August 2020. We measured the skeletal muscle and adipose tissue of all patients at the level of the third lumbar vertebra on plain abdominal computed tomography (CT) images and subsequently derived an equation via least absolute shrinkage and selection operator (LASSO) regression analysis to calculate the sarcopenia score. Univariate and multivariate regression were performed to reveal the relationship between major postoperative complications and perioperative clinical data, and the obtained nomogram was validated with the bootstrapping method.ResultsThe sarcopenia score was constructed as a personalized indicator to evaluate sarcopenia and visceral adiposity in each patient. Logistic regression analysis finally selected duration from primary diagnosis to obvious symptoms (OR=1.024, 95% CI, 1.007–1.042), surgical time (OR=1.003, 95% CI, 0.999–1.007) and sarcopenia score (OR=4.283, 95% CI, 1.739–10.551) as independent risk factors for predicting major postoperative complications following ELRA for end-stage HAE patients. The area under the receiver operating characteristic curve (AUROC) of 0.807 (95% CI, 0.720–0.895) and the calibration curve for this prediction model were satisfactory.ConclusionThe sarcopenia score, which systematically evaluates the skeletal muscle and adipose tissue of end-stage HAE patients, was a significant predictive factor for major postoperative complications of ELRA. Relevant interventions should be conducted for those who have a high risk of postoperative complications according to the nomogram.

Possible Involvement of Adipose Tissue in Patients With Older Age, Obesity, and Diabetes With SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19.

Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium–glucose cotransporter 2 inhibitor, or β3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.

Inflammasome activation in epicardial, pericardial and subcutaneous adipose tissue in patients with coronary heart disease

Abstract Background The adipose tissue (AT) compartments surrounding the heart have been claimed to exert different pro-inflammatory properties with different associations with cardiovascular disease states. The epicardial AT (EAT), located close to the coronary arteries between the myocardium and the pericardial layer, seems to be associated with atherosclerosis and metabolic syndrome, whereas the pericardial AT (PAT), separated from the heart by the pericardium, is discussed to have less pro-inflammatory properties. Purpose The aim of the present study was to explore any differences in genetic regulation of pro-inflammatory markers included in the inflammasome related pathway in EAT, PAT and in subcutaneous AT (SAT). In addition, any relationship to the corresponding inflammatory markers in the circulation was explored. Materials and methods Biopsies from EAT, PAT and SAT, and arterial blood samples were collected from 52 patients with coronary heart disease (CHD) undergoing coronary by-pass surgery (aged 48–82 years, 70% male, median body mass index (BMI) 27.3 kg/m2). RNA was extracted by use of RNeasy Lipid Tissue Mini Kits. Gene expression of Interleukin (IL)-1β, IL-18, NLRP3, Caspase-1, toll-like receptor 4 (TLR4), IL-6, IL-6 receptor and gp130 in the different adipose tissue compartments were analyzed using RT-PCR. Circulating levels where possible, were measured in serum with ELISAs. Results We demonstrated that IL-18 and IL-6 were about 4-fold higher expressed in EAT compared to PAT (p&amp;lt;0.01, both) and SAT (p&amp;lt;0.001, both), whereas Caspase-1, IL-6R and gp130 were higher expressed in SAT compared to the other compartments (all p 0.06 - &amp;lt;0.001). TLR4 was significantly higher expressed in PAT compared to EAT (p=0.01) and SAT (p&amp;lt;0.001). No differences in the expression of IL-1β and NLRP3 were found. We could further demonstrate significant correlations between SAT and PAT expression of all the measured genes (r=0.358–0.579, all p≤0.01), except TLR4. No significant correlations between circulating levels and the genetic expression in either AT compartments were observed, and also limited correlations to BMI. Conclusions The results shows that only IL-18 and IL-6 were higher expressed in EAT, compared to the two other AT compartments in our non-obese CHD population. The results further show that the inflammasome related genes in pericardial AT associated strongly with subcutaneous AT, suggesting SAT to be more pro-inflammatory than previously expected. Funding Acknowledgement Type of funding sources: None.

Activation of the Adipose Tissue NLRP3 Inflammasome Pathway in Cancer Cachexia.

BackgroundCachexia is a paraneoplastic syndrome that accompanies and compromises cancer treatment, especially in advanced stages, affecting the metabolism and function of several organs. The adipose tissue is the first to respond to the presence of the tumor, contributing to the secretion of factors which drive the systemic inflammation, a hallmark of the syndrome. While inflammation is a defensive innate response, the control mechanisms have been reported to be disrupted in cachexia. On the other hand, little is known about the role of NLRP3 inflammasome in this scenario, a multiprotein complex involved in caspase-1 activation and the processing of the cytokines IL-1β and IL-18.Aimbased on the evidence from our previous study with a rodent model of cachexia, we examined the activation of the NLRP3 inflammasome pathway in two adipose tissue depots obtained from patients with colorectal cancer and compared with that another inflammatory pathway, NF-κB.ResultsFor CC we found opposite modulation in ScAT and PtAT for the gene expression of TLR4, Caspase-1 (cachectic group) and for NF-κB p50, NF-κB p65, IL-1β. CD36, expression was decreased in both depots while that of NLRP3 and IL-18 was higher in both tissues, as compared with controls and weight stable patients (WSC). Caspase-1 basal protein levels in the ScAT culture supernatant were higher in WSC and (weight stable patients) CC, when compared to controls. Basal ScAT explant culture medium IL-1β and IL-18 protein content in ScAT supernatant was decreased in the WSC and CC as compared to CTL explants.ConclusionsThe results demonstrate heterogeneous responses in the activation of genes of the NLRP3 inflammasome pathway in the adipose tissue of patients with cancer cachexia, rendering this pathway a potential target for therapy aiming at decreasing chronic inflammation in cancer.

Hypoxic preconditioning promotes survival of human adipocyte mesenchymal stem cell via expression of prosurvival and proangiogenic biomarkers

Background: Contributing factors for improved survival of human adipocytes mesenchymal stem cells (h-AMSCs) cultured through hypoxia preconditioning, in example apoptosis inhibition involving BCL2 and HSP27 expression, trigger signal expression (VEGF), SCF expression, OCT-4 expression, and CD44+ expression. The objective if this study was to explain the mechanism and role of hypoxic preconditioning and the optimal duration of hypoxic preconditioning exposure to improve survival of h-AMSCs. Methods: An experimental laboratory explorative study (in vitro) with hypoxic preconditioning in h-AMSCs cultures. This research was conducted through four stages. First, isolation of h-AMSCs culture from adipose tissue of patients. Second, the characterization of h-AMSCs from adipose tissue by phenotype (flowcytometry) through CD44+, CD90+ and CD45-expression before being pre-conditioned for hypoxic treatment. Third, the hypoxic preconditioning in h-AMSCs culture (in vitro) was performed with an oxygen concentration of 1% for 24, 48 and 72 hours. Fourth, observation of survival from h-AMSCs culture was tested on the role of CD44+, VEGF, SCF, OCT-4, BCL2, HSP27 with Flowcytometry and apoptotic inhibition by Tunnel Assay method. Results: The result of regression test showed that time difference had an effect on VEGF expression (p&lt;0.001;β=-0.482) and hypoxia condition also influenced VEGF expression (p&lt;0.001;β=0.774). The result of path analysis showed that SCF had effect on OCT-4 expression (p&lt;0.001; β=0.985). The regression test results showed that time effects on HSP27 expression (p&lt;0.001; β=0.398) and hypoxia precondition also affects HSP27 expression (p&lt;0.001; β=0.847). Pathway analysis showed that BCL2 expression inhibited apoptosis (p=0.030; β=-0.442) and HSP27 expression also inhibited apoptosis (p&lt;0,001;β=-0.487). Conclusion: Hypoxic preconditioning of h-AMSC culture has proven to increase the expression of VEGF, SCF, OCT-4, and BCL2 and HSP27. This study demonstrated and explained the existence of a new mechanism of increased h-AMSC survival in cultures with hypoxic preconditioning (O2 1%) via VEGF, SCF, OCT-4, BCL2, and HSP 27.