Adipose Tissue-derived Cells Research Articles

Genetically Engineered Clostridium Prevents Perivascular Adipose Tissue and Endothelial Senescence and Dysfunction in Aging

Abstract Introduction (Peri)vascular senescence is a bona fide risk for several aging-associated diseases that threatens healthspan. Gut microbiome may be one of triggers that promotes vascular diseases as host ages. However, the interplay between vascular senescence and gut microbiome is largely unknown. Our recent studies revealed an increase in gut-derived phenylacetic acid (PAA) in the aging population (TwinsUK Aging Cohort, n=7,303) and aged mice. Our preliminary shotgun metagenomics also showed that ppfor-harboring Clostridium sp. ASF356 age-dependently generates PAA, which induces perivascular adipose tissue (PVAT) and endothelial cell (EC) senescence and dysfunction in old mice. Yet, it remains unclear whether and how genetic engineering of Clostridium sp. ASF356 (by depleting ppfor gene) can prevent aortic PVAT-EC senescence and restore vascular function in aging. Methods For bacterial genetic engineering, we depleted ppfor gene in Clostridium ASF356 by ClosTron technique and further mono-colonized aged mice (24-months old) and germ-free mice, as control, to reduce plasma PAA and thereby prevent aortic PVAT-EC senescence and improve endothelial dysfunction. Results As a proof of the concept, our studies exhibited that mono-colonization of germ-free mice with wild-type Clostridium sp. ASF356 markedly elevates plasma PAA levels. It was accompanied by hallmarks of aortic PVAT-EC senescence, including increased DNA damage (↑ γ-H2A.X phosphorylation), heightened SASP (↑ IL-6 and VCAM1), and proliferative arrest (↑ p16INK4a and p21WAF1/Cip1). Additionally, our findings revealed upreglation of Notch1 in PVAT, contributing to reduced energy supply (↓ UCP1) and augmented senescence-messaging secretome (↑ IL-6) towards ECs. Our further studies revealed that mono-colonization of aged mice (pre-treated with antibiotics) with Δppfor Clostridium ASF356 mutants intriguingly resulted in decreased plasma PAA levels. This intervention led to the rescues of cellular senescence in both aortic PVAT and ECs, consequently improving vascular function. Specifically, mice subjected to this treatment exhibited a significant reduction in SA-β-galactosidase+ cells, as well as decreased levels of γ-H2A.X phosphorylation, p16INK4a, p21WAF1/Cip1, and IL-6 in their aortic PVAT and ECs compared to wild-type aged mice. Conclusions The current study suggests that genetically engineered Δppfor Clostridium ASF356 mutants reverse cellular senescence and restore function in aortic PVAT and endothelial cells, highlighting the potential for targeted gut microbiome manipulation as an innovative senotherapy to combat vascular aging.

MicroRNA Expression in Chronic Venous Leg Ulcers and Implications for Wound Healing: A Scoping Review.

Purpose: Chronic venous leg ulcers (CVLUs) comprise the majority of lower-extremity wounds, yet their pathophysiology is not fully understood. While research has shown that microRNAs are an important component of wound inflammation, few have explored the role of microRNAs (miRNAs) in the healing of CVLUs. This scoping review examines miRNAs in CVLUs and the association with wound healing. Methods: In December 2023, we searched MEDLINE/PubMed, Embase, Scopus, and CINAHL for studies published in 2013-2023 examining miRNAs in CVLU healing. Results: Six studies met inclusion criteria. MicroRNAs were extracted from various specimens including serum, skin biopsy samples, and adipose tissue-derived mesenchymal cells from individuals with CVLUs. Overexpression of miR-221, miR-222, miR-92a, and miR-301a-3p hindered angiogenesis, while overexpression of miR-296, miR-126, miR-378, and miR-210 facilitated angiogenesis. Overexpression of miR-34a/c, miR-301a-3p, miR-450-5p, miR-424-5p, miR-516-5p, and miR-7704 increased local inflammatory responses and inhibited keratinocytes proliferation, impairing healing, while overexpression of miR-19a/b and miR-20 downregulated keratinocytes' inflammatory response, promoting healing. Downregulation of miR-205, miR-96-5p, and miR-218-5p enhanced cellular proliferation and promoted wound healing. Downregulation of miR-17-92 was linked with impaired healing. Discussion: MicroRNAs play a role in regulating angiogenesis, inflammatory responses, and cell migration in chronic-wound healing. However, studies of miRNAs in CVLUs are limited and lack a standardized approach to measurement and quantification. Further research is warranted to elucidate the mechanisms underlying microRNA involvement in CVLU healing to better understand the pathophysiology and for the future development of targeted therapies.

Adipose tissue responds to stress-induced immunosuppression affecting immune response partially by miR-145-5p/S1PR1 pathway

Stress-induced immunosuppression (SIIS) is one of the most common problems in intensive poultry production, which can cause immunized chickens to still develop diseases and bring huge losses to production. Recently, adipose tissue, as an immunomodulatory organ, has become a hot topic of attention. However, the function and mechanism of adipose tissue involved in SIIS and its influence on the immune response are still unclear. In this study, we dynamically analyzed the correlations between the T cells migration and change of sphingosine-1-phosphate receptor 1(S1PR1) gene in adipose tissue using chicken models with different immune states, and further explored the regulatory mechanisms and application. The results showed that SIIS could significantly change the expressions of lymphocytes migration related S1PR1 gene, and SIIS could inhibit the Newcastle disease virus (NDV) immune response partially by affecting the migration and proliferation of TCRα+ T cells in adipose tissue. Moreover, the miR-145-5p/S1PR1 pathway was a potential key mechanism to regulate T cells migration in adipose tissue, and circulating miR-145-5p had potential value as a molecular marker. This research can provide innovative reference for in-depth studying the immunoregulatory function and mechanism of adipose tissue.

Hypomethylation at PANDAR promoter progressively induces senescence in adipocyte precursor cells in subjects with obesity and type 2 diabetes.

The risk of developing type 2 diabetes (T2D) is heterogeneous among individuals with obesity. Functional decline of adipocyte precursor cells (APCs) and accumulation of senescent cells in the subcutaneous adipose tissue contributes to the progression toward T2D. LncRNAs regulate cell senescence and may be implicated in determining this abnormality in APCs. Here, we report that APCs from individuals with obesity show a gradual increase in multiple senescence markers, which worsens in parallel with the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) or T2D. Transcriptomic analysis identified PANDAR as the top-ranked lncRNA differentially expressed in APCs from individuals with obesity and T2D and non-obese subjects. Q-PCR confirmed PANDAR up-regulation in APCs from individuals with obesity, at progressively increased levels in those who developed, respectively, IGT and T2D. Bisulfite sequencing and luciferase assays revealed that, in parallel with glucose tolerance deterioration, the -1317 CpG at the PANDAR promoter became hypo-methylated in obesity, resulting in enhanced PANDAR induction by p53. PANDAR silencing in senescent APCs from individuals with obesity and T2D caused repression of senescence programs and cell cycle re-entry. PANDAR transcription in white blood cells (WBCs) mirrored that in APCs. Also, individuals with obesity exhibited rescue of PANDAR transcription in WBCs following bariatric surgery, accompanied by enhanced methylation at the regulatory PANDAR -1317 CpG. In conclusion, PANDAR dysregulation is a newly identified mechanism determining the early senescence of APCs from individuals with obesity, which worsens along the progression toward T2D. In the future, PANDAR targeting may represent a valuable strategy to delay this progression.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

The Role of Omentin-1 and Fibroblast Growth Factor-23 in Iraqi Patients with Prostate Cancer during Chemotherapy

Background: Omentin-1 is mainly expressed in stromal vascular cells of adipose tissue and can also be expressed in airway goblet cells, mesothelial cells, and vascular cells. Fibroblast growth factor 23 (FGF-23), generated by bone cells, regulates phosphate and vitamin D metabolism by regulating phosphate reabsorption in the kidneys and inhibiting vitamin D activation. Vitamin D is a fat-soluble vitamin that regulates calcium absorption, bone health, and immunological function. Prostate cancer is a significant health concern for men worldwide. Several studies demonstrated a link between these variables and cancer as they exert important anti-inflammatory, antioxidative, and anti-cancer functions. Objectives: To assess the impact of Omentin and FGF-23 biochemical functions, as well as the anti-cancer properties of vitamin D. Subjects and methods: This is a case-control study on serum samples collected from Iraqi prostate cancer patients after receiving chemotherapy at Al Amal Center in Imam Hussein Medical City in Karbala between November 2022 to May 2023. The serum samples were collected from two groups: control group consisted of 30 healthy males. Patient group consisted of 30 prostate cancer patients after receiving chemotherapy, both groups aged 45 – 80 years. The two groups were matched for body mass index. ELISA technology was used to estimate serum levels of the aforementioned biochemical parameters with vitamin D. Results: patient group had a significantly higher FGF-23 level than control group (309.5±41.65) versus (163.1±22.4) (p<0.001). On the other hand, Irisin, Omentin and Vitamin D mean serum concentrations were significantly lower in-patient group (15.2±4.24), (13.8±4.28) and (4.4±0.69) (p<0.001), respectively, compared to control group (60.8±3.5), (38.8±6.59), and (18.9±2.36), respectively. (ROC) curve analysis identified the best AUC values of FGF-23, Omentin, and Vitamin D (0.995, 0.959, 0.937), respectively, which suggests a high level of accuracy. Conclusions: These parameters may serve as critical indicators for prostate cancer patients and their disease progress. Vitamin D insufficiency is a risk factor for these individuals.

Oct-B: A derivative of L-BAIBA significantly alleviating high-fat diet-induced obesity in mice

The rising prevalence of obesity is a global health concern. Supplementation with (S)-β-aminoisobutyric acid (L-BAIBA) has shown potential in preventing obesity and related metabolic disorders induced by high-fat diets. However, developing effective and low-toxicity BAIBA derivatives remains a challenging yet promising field. In this study, we introduce Oct-B, a novel BAIBA ester compound, which exhibits 80-fold greater efficacy than L-BAIBA in alleviating obesity in high-fat diet-fed mice. Our results demonstrate that Oct-B significantly reduces serum TG, TC, LDL-C, and the activities of ALT and AST, and also reduces TG and TC in liver, surpassing the effects of L-BAIBA. Histological analysis shows that Oct-B significantly decreases lipid accumulation in liver tissues, normalizes mast cells in white adipose tissue, and upregulates the expression of UCP1 protein in white adipose tissue. The qRT-PCR results indicated Oct-B alleviates obesity by downregulating lipogenic genes (PPARγ, ACC1, FAS), upregulating lipolysis related genes (PPARα, HSL) and thermogenic gene UCP1. Additionally, quantitative mass spectrometry reveals a marked increase in L-BAIBA levels in white fat, brown fat, serum, and muscle following Oct-B administration. These findings suggest that Oct-B is an efficient L-BAIBA substitute, offering a promising therapeutic approach for preventing and treating high-fat diet-induced obesity.

Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution.

Overall adiposity and body fat distribution are heritable traits associated with altered risk of cardiometabolic disease and mortality. Performing rare variant (minor allele frequency<1%) association testing using exome-sequencing data from 402,375 participants in the UK Biobank (UKB) for nine overall and tissue-specific fat distribution traits, we identified 19 genes where putatively damaging rare variation associated with at least one trait (Bonferroni-adjusted P<1.58×10-7) and 52 additional genes at FDR≤1% (P≤4.37×10-5). These 71 genes exhibited higher (P=3.58×10-18) common variant prioritisation scores than genes not significantly enriched for rare putatively damaging variation, with evidence of monotonic allelic series (dose-response relationships) among ultra-rare variants (minor allele count≤10) in 22 genes. Five of the 71 genes have cognate protein UKB Olink data available; all five associated (P<3.80×10-6) with three or more analysed traits. Combining rare and common variation evidence, allelic series and proteomics, we selected 17 genes for CRISPR knockout in human white adipose tissue cell lines. In three previously uncharacterised target genes, knockout increased (two-sided t-test P<0.05) lipid accumulation, a cellular phenotype relevant for fat mass traits, compared to Cas9-empty negative controls: COL5A3 (fold change [FC]=1.72, P=0.0028), EXOC7 (FC=1.35, P=0.0096), and TRIP10 (FC=1.39, P=0.0157); furthermore, knockout of SLTM resulted in reduced lipid accumulation (FC=0.51, P=1.91×10-4). Integrating across population-based genetic and in vitro functional evidence, we highlight therapeutic avenues for altering obesity and body fat distribution by modulating lipid accumulation.

Cytokine and chemokine receptor profiles in adipose tissue vasculature unravel endothelial cell responses in HIV.

Chronic systemic inflammation significantly increases myocardial infarction risk in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis, contributing to cardiovascular disease. We aimed to characterize endothelial cell (EC) chemokines, cytokine, and chemokine receptors of PLWH, hypothesizing that in our cohort, glucose intolerance contributes to their differential expression implicated in endothelial dysfunction. Using single-cell transcriptomic analysis, we phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in subcutaneous adipose tissue of 59 PLWH with and without glucose intolerance. Our results show that arterial and capillary ECs express significantly higher interferon and tumor necrosis factor (TNF) receptors than venous ECs and VSMCs. Venous ECs exhibited more interleukin (IL)1R1 and ACKR1 receptors, and VSMCs showed significant IL6R expression than arterial and capillary ECs. When stratified by group, arterial ECs from PLWH with glucose intolerance expressed significantly higher IL1R1, IL6R, CXCL12, CCL14, and ICAM2 transcripts than arterial ECs from PLWH without diabetes. Of the different vascular cell types studied, arterial ECs as a proportion of all ECs in adipose tissue were positively correlated with plasma fasting blood glucose. In contrast, venous ECs and VSMCs were positively correlated with plasma IL6. To directly assess the effect of plasma from PLWH on endothelial function, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk RNA sequencing. Plasma from PLWH stimulated ECs with the upregulation of genes that enrich for the oxidative phosphorylation and the TNF-α via NFK-β pathways. In conclusion, ECs in PLWH show heterogeneous cytokine and chemokine receptor expression, and arterial ECs were the most influenced by glucose intolerance. Further research must explicate cytokine and chemokine roles in EC dysfunction and identify biomarkers for disease progression and therapeutic response.

Interleukin-27 signaling resists obesity by promoting the accumulation of Treg cells in visceral adipose tissue

The prevalence of obesity and its associated metabolic disorders has emerged as one of the most significant health threats worldwide. The visceral adipose tissue regulatory T cells (VAT Treg) play an essential role in maintaining homeostasis and preventing obesity mainly by secreting Interleikin-10 (IL-10) and Transforming Growth Factor β (TGF-β). However, the mechanism that regulates VAT Treg quantity and function remains unclear. Here we elucidate the pivotal role of IL-27 signaling in sustaining the accumulation of VAT Treg cells, thereby conferring protection against obesity. We found that mice with the deficiency of IL-27 receptor Wsx1 gained more body weight and VAT weight than their wild-type littermates when fed both a normal-fat diet (NFD) and a high-fat diet (HFD). Notably, the population of VAT Treg cells was reduced in Wsx1 knockout (KO) mice, regardless of whether they were fed a normal-fat diet (NFD) or a high-fat diet (HFD). Correspondingly, the expression levels of the transcription factors FOXP3 and PPAR-γ, essential for VAT Treg function, were also diminished in Wsx1 KO mice. Taken together, our findings indicate that IL-27 signaling plays a protective role in obesity by supporting the maintenance and accumulation of VAT Treg cells.

Lespedeza homoloba enhances the immunosuppressive milieu of adipose tissue and suppresses fasting blood glucose.

Immune cells migrate to hypertrophied adipocytes and release proinflammatory cytokines, leading to adipocyte dysfunction and diabetes. Numerous species of Lespedeza, which are members of the plant family Fabaceae and distributed primarily in temperate Asia and North America, exhibit binding to peroxisome proliferator-activated receptor (PPAR) γ, a target nuclear receptor for treating diabetes. Therefore, the present study aimed to determine which species of Lespedeza plants exert an anti-inflammatory effect in adipose tissue and suppression of blood glucose increase through PPARγ ligand and radical scavenging activity. PPARγ binding and DPPH radical scavenging assays of L. homoloba (LH), L. thunbergii (LT), L. maximowiczii (LM) and L. thunbergii (LT) were performed. LH and LT showed significant ligand activity towards PPARγ and notable radical scavenging activity. LH exhibited a stronger DPPH radical scavenging activity than LT and thus was measured adiponectin secretion from 3T3-L1-derived adipocytes and IL-10 secretion from murine splenocytes. LH increased the adiponectin and the IL-10 secretions. In flow cytometric analysis, BALB/c male mice administered LH exhibited an increase in regulatory T cells (Tregs) and cytotoxic T lymphocyte-associated protein (CTLA)-4+ Tregs as well as a decrease in T helper (Th)17, Th17/Treg ratio and CD8+ and CD4+ T cells in subcutaneous adipose tissue. Conversely, in the spleen, LH decreased Tregs and increased Th17 cells, Th17/Treg ratio and CD4+ and CD8+ T cells. These findings indicated that LH activated immunoreaction in the spleen and Treg cells that migrate to subcutaneous adipose tissue may suppress inflammation. In fasting blood glucose and adiponectin assays, LH-exposed mice exhibited suppression of fasting glucose levels. Therefore, LH may prevent type 2 diabetes by suppressing adipose tissue inflammation.

Hinokiflavone resists HFD-induced obesity by promoting apoptosis in an IGF2BP2-mediated Bim m6A modification dependent manner

Obesity has emerged as a major health risk on a global scale. Hinokiflavone (HF), a natural small molecule, extracted from plants like cypress, exhibits diverse chemical structures and low synthesis costs. Using high-fat diet (HFD)-induced obese mice models, we found that HF suppresses obesity by inducing apoptosis in adipose tissue. Adipocyte apoptosis helps maintain tissue health by removing aging, damaged, or excess cells in adipose tissue, which is crucial in preventing obesity and metabolic diseases. We found that HF can specifically bind to insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to promote the stability of N6-methyladenosine (m6A) -modified Bim, inducing mitochondrial outer membrane permeabilization (MOMP). MOMP leads to Caspase9/3-mediated adipocyte mitochondrial apoptosis, alleviating obesity induced by a high-fat diet. The pro-apoptotic effect of HF offers a controlled means for weight loss. This study reveals the potential of small molecule HF in developing new therapeutic approaches in drug development and biomedical research.

Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.

Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns1. Here we uncover the mechanism by which NPY in sympathetic neurons2,3 protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY+ sympathetic axons are a smallersubset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains the proliferation ofmural cells, which are a source of thermogenic adipocytes in both BAT and WAT4-6. We found that diet-induced obesity leads to neuropathy of NPY+ axons and concomitant depletion of mural cells. This defect was replicated in mice with NPY abrogated from sympathetic neurons. The loss of NPY in sympathetic neurons whitened interscapularBAT, reducing itsthermogenic ability and decreasing energy expenditure before the onset of obesity. It also caused adult-onset obesity of mice fed on a regular chow diet and rendered them more susceptible to diet-induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.

Enrichment of novel CD3+F4/80+ cells in brown adipose tissue following adrenergic stimulation.

Macrophages play a multifaceted role in maintaining tissue homeostasis, fighting infections, and regulating cold-induced thermogenesis. The brown adipose tissue (BAT) is crucial for maintaining body temperature during cold exposure. Cold stress triggers the sympathetic nervous system to release norepinephrine (NE), which activates BAT via β3-adrenergic receptors, initiating lipolysis and glycolysis. BAT-infiltrating macrophages can either hinder or enhance thermogenesis by controlling the interplay between BAT cells and sympathetic nerves. In this study we report on a unique population of CD3+F4/80+ dual lineage co-expressing (DE) cells within the interscapular BAT (iBAT), that increased following chronic adrenergic stimulation. In forward scatter/side scatter plots, they formed a cluster distinct from lymphocytes, appearing larger and more complex. These CD3+F4/80+ DE cells demonstrated the lack of T cell markers CD62L and TCRβ and expressed higher levels of Ly6C, F4/80, and CD11b markers compared to T cells and CD3- macrophages. Furthermore, analysis revealed two subpopulations within the CD3+F4/80+ DE population based on MHCII expression, with the proportion of MHCII-low subset increasing with adrenergic stimulation. This novel DE population within iBAT, unequivocally identified by the its unique surface marker profile, warrants further investigation into the intricate mechanisms governing adaptive thermogenesis regulation.

Mesenchymal stem cells from adipose tissue prone to lose their stemness associated markers in obesity related stress conditions

Obesity is a health problem characterized by large expansion of adipose tissue. During this expansion, genotoxic stressors can be accumulated and negatively affect the mesenchymal stem cells (MSCs) of adipose tissue. Due to the oxidative stress generated by these genotoxic stressors, senescence phenotype might be observed in adipose tissue MSCs. Senescent MSCs lose their proliferations and differentiation properties and secrete senescence-associated molecules to their niche thus triggering senescence for the rest of the tissue. Accumulation of senescent cells in adipose tissue results in decreased tissue regeneration and functional impairment not only in the close vicinity but also in the other tissues. Here we hypothesized that declined tissue regeneration might be associated with loss of stemness markers in MSCs population. We analyzed the expression of several stemness-associated genes of in vitro cultured MSCs originated from adipose tissue of high-fat diet and normal diet mice models. Since the heterogenous MSCs population covers a small percentage of the pluripotent stem cells, which have roles in proliferation and tissue regeneration, we measured the percentage of these cells via TRA-1-60 pluripotent state antigen. Additionally, by conducting a shotgun proteomic approach using LC-MS/MS, whole cell proteome of the adipose tissue MSCs of high-fat diet and normal diet mice were analyzed and identified proteins were evaluated via gene ontology and PPI network analysis. MSCs of obese mice showed senescent phenotype and altered cell cycle distribution due to a hostile environment with oxidative stress in adipose tissue where they reside. Additionally, the number of pluripotent markers expressing cells declined in the MSC population of the high-fat diet mice. Gene expression analysis evidenced the loss of stemness with a decrease in the expression of stemness-associated genes. Of the proteomic comparison of the normal and the high-fat diet group, MSCs revealed that stemness-associated molecules were decreased while inflammation and senescence-associated phenotypes emerged in obese mice MSCs. Our results showed us that the MSCs of adipose tissue may lose their stemness properties due to obesity-associated stress conditions.

Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.

An Investigation of Substances Influencing Adipocyte Function

Adipose tissue plays a central metabolic role in systemic energy metabolism via nutrient exchange and secretion of adipose-derived hormones and cytokines. Adipose tissue dysfunction increases the risk of developing conditions, including type 2 diabetes, coronary artery disease, stroke, and cancer, ultimately shortening healthy lifespan. Maintaining adipose tissue functions has recently garnered attention as a means to extend healthy life expectancy. We previously developed a T-cell activation-inhibitory assay, which facilitates efficient selection of candidate substances for extending healthy lifespan. Using this assay, we identified two candidate substances: Cynandione A (CA), a major component of Cynanchum wilfordii, and N-caffeoyltryptophan (NCT) found in coffee. This review summarizes recent findings regarding the effect of CA and NCT on adipocyte (the primary cells in adipose tissue) function, and their potential contribution to extending healthy life expectancy.

Effect of bariatric surgery in the body burden of persistent and non-persistent pollutants: longitudinal study in a cohort of morbidly obese patients.

Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology. To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes. GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery. Detection rates of p,p'-DDE, HCB, β-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p'-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods. Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.

The safety and efficacy of adipose tissue-derived exosomes in treating mild to moderate plaque psoriasis: A clinical study

AimThis study evaluates the safety and efficacy of autologous adipose-derived mesenchymal stem cell-derived exosomes as a treatment for Psoriasis, a chronic immune-related skin and joint disorder, compared to current treatments like topicals, phototherapy, and systemic. Materials and methodsThe study isolated exosomes from Mesenchymal Stem Cells(MSCs) of healthy adipose tissue using ultracentrifugation. 12 patients with plaque psoriasis were divided into three groups and given single doses of exosomes. Tissue samples were collected pre- and post-treatment and examined for inflammatory(TNFα, IL23, IL17, IFNγ, CD3) and anti-inflammatory (FOXP3, IL10) markers. The severity of the lesion was also evaluated. Key findingsIn this study, it was found that erythema and induration (P < 0.05) decreased significantly in patients receiving 200 μg. Still, this reduction in scaling was not significant, the thickness was significantly reduced in patients receiving 100 and 200 μg doses (P < 0.05). H&E evaluation showed that the decreasing trend in these patients was not significant (P > 0.05). IHC evaluation in patients receiving doses of 100 and 200 μg showed a decrease in the presence of IL17 (P < 0.05, <0.001) & CD3(P < 0.001, <0.05) and a considerable increase in FOXP3(P ≤ 0.001), in the tissue samples of the patients. Examining the expression of inflammatory factors also shows that dose 200 μg decreased the expression of IL17(P > 0.05), IFNγ(P > 0.05), IL23(P < 0.05), & TNFα(P ≤ 0.05) and increased the expression of the anti-inflammatory factor IL10(P < 0.05). SignificanceThe study indicates that a 200 μg dose is optimal for patients, but a larger patient population is needed for more reliable results. Additionally, higher doses or multiple injections with specific intervals can increase confidence.

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

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