Adipocyte最新文献

Graves' orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p < 0.0001). AIF-1 was significantly associated with the presence of GO after adjusting for clinical factors (age, sex, smoking and BMI) and level of TSH (odds ratio 1.003, p < 0.01). This finding could enforce targeting macrophages in treatment strategies for GO since AIF-1 is considered as a marker of their activation.

Vaspin expression and function is related to metabolic disorders and comorbidities of obesity. In various cellular and animal models of obesity, diabetes and atherosclerosis vaspin has shown beneficial, protective and/or compensatory action. While testing proteases for inhibition by vaspin, we noticed specific cleavage within the vaspin N-terminus and sequence analysis predicted cell-penetrating activity for the released peptides. These findings raised the question whether these proteolytic peptides exhibit biological activity.We synthesized various N-terminal vaspin peptides to investigate cell-penetrating activity and analyse uptake mechanisms. Focusing on adipocytes, we performed microarray analysis and functional assays to elucidate biological activities of the vaspin-derived peptide, which is released by KLK7 cleavage (vaspin residues 21-30; VaspinN). Our study provides first evidence that proteolytic processing of the vaspin N-terminus releases cell-penetrating and bioactive peptides with effects on adipocyte biology. The VaspinN peptide increased preadipocyte proliferation, interfered with clonal expansion during the early stage of adipogenesis and blunted adrenergic cAMP-signalling, downstream lipolysis as well as insulin signalling in mature adipocytes.Protease-mediated release of functional N-terminal peptides presents an additional facet of vaspin action. Future studies will address the mechanisms underlying the biological activities and clarify, if vaspin-derived peptides may have potential as therapeutic agents for the treatment of metabolic diseases.

Human adipose-derived stem cells (hADSCs) are adult mesenchymal cells that have attracted the interest of clinical scientists and surgeons due to their large number of advantages including ease of access and expansion, abundance in cell culture, high proliferative rates, and lower senescence. SUMO/sentrin specific protease 1 (SENP1) is a critical protease that is required during the process of SUMOylation and deSUMOylation, which are dynamic mechanisms that influence cell cycle progression, cell proliferation, and apoptotic status. However, the contribution of SENP1 to these important cellular processes in hADSCs is largely uncharacterized and further studies in this area are required. Here, we show for the first time that after knock out SENP1 in hADSCs, their capacity to migrate and proliferate were inhibited, while apoptosis was enhanced. However, SENP1 did not significantly influence the morphology and MSC-related phenotypes of the hADSCs. These results highlight a role for SENP1 during hADSC growth, and its potential as a therapeutic target to improve the efficacy and safety of hADSCs in the clinic.

Increasing evidence shows that immune-related genes (IRGs) play an important role in bariatric surgery (BS). We identified differentially expressed immune-related genes (DEIRGs) of adipose tissue after BS by analysing the two expression profiles of GEO (GSE59034 and GSE29409). Subsequently, enrichment analysis, GSEA and PPI networks were examined to identify the hub IRGs and related pathways. The performance of the signature was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC). CIBERSORT algorithm was used to evaluate the relative abundance of infiltrated immune cells.42 DEIRGs were found between the GSE59034 and GSE29409 datasets. The AUC of the signature was 0.904 and 0.865 in the GSE58979 and GSE48452, respectively. Interestingly, the signature also showed good performance in diagnosing non-alcoholic fatty liver disease (NAFLD) (AUC was 0.834 and 0.800, respectively). The number of neutrophils, macrophages M2, macrophages M0 and dendritic cells activated decreased significantly. After BS, the infiltration of T cells regulatory, monocytes, mast cells resting and plasma cells in adipose tissue increased. The novel proposed IRGs signature reveals the underlying immune mechanism of BS and is a promising biomarker for distinguishing the severity of NAFLD. This will provide new insights into strategies for treating obesity and NAFLD.

Recent studies showed that exosomes obtained from adipose-derived stem cells (ADSCs) could improve the angiogenesis of fat grafts via overexpression of vascular endothelial growth factor (VEGF). Human antigen R (HuR) promotes the expression of VEGF in many cancers, but the effect of HuR in normal endothelial cells in the presence of ADSC-derived exosomes remains unclear. We aimed to investigate the effect of HuR on the expression of VEGF and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with ADSCs-derived exosomes. The HuR-overexpressed HUVECs (HuR-HUVECs) were cocultured with ADSCs-derived exosomes. qRT-PCR and Western blotting were performed to examine the stability and expression of VEGF-A mRNA and protein. The proliferation, migration, and proangiogenic capacity of HuR-HUVECs were evaluated using cell counting kit-8 (CCK-8), scratch wound healing, and Matrigel tube formation assay. qRT-PCR showed that HuR-HUVECs had higher expression and slower attenuation of VEGF-A mRNA. Western blotting confirmed higher expression of VEGF-A in HuR-HUVECs. CCK-8, scratch wound healing, and Matrigel tube formation assay demonstrated an increased proangiogenic effect in HuR-HUVECs. HuR promotes angiogenesis of HUVECs cocultured with ADSCs-derived exosomes via stabilization and overexpression of VEGF in vitro. The HuR/VEGF pathway is an important regulatory mechanism of angiogenesis in endothelial cells.

Compared to body mass index, waist circumference (WC), and adiposity measurements, adipose tissue (AT) morpho-functionality evaluations are better predictors of cardiometabolic abnormalities (CA). The present study establishes a dysfunctional adiposity index (DAI) as an early marker of CA based on adipocytes morpho-functional abnormalities. DAI was established in 340 subjects without cardiovascular risk factors selected from a cross-sectional study (n=1600). Then, DAI was calculated in 36 healthy subjects who underwent subcutaneous AT biopsy. The correlation of DAI with adipocyte morphology (size/number) and functionality (adiponectin/leptin ratio) was analyzed. The DAI cut-off point was identified and its independent association with CA was determined in 1418 subjects from the cross-sectional study. The constant parameters to calculate the DAI were [WC/[22.79+[2.68*BMI]]]*[triglycerides (TG, mmol/L)/1.37]*[1.19/high density lipoprotein-cholesterol (HDL-C, mmol/L)] for males, and [WC/[24.02+[2.37*BMI]]]*[TG(mmol/L)/1.32]*[1.43/HDL-C(mmol/L)] for females. DAI correlated with adipocytes mean area, adipocyte number and adiponectin/leptin ratio. DAI ≥1.065 was independently associated with diabetes, non-alcoholic fatty liver disease, subclinical atherosclerosis, and hypertension. The present study highlights that DAI is associated with early CA independently of adiposity and other risk factors. Since DAI is obtained using accessible parameters, it can be easily incorporated into clinical practice for early identification of AT abnormalities in apparently healthy subjects.

Preadipocyte proliferation is a critical and precisely orchestrated procedure in adipogenesis, which is highly regulated by microRNAs (miRNAs). A previous study identified that the expression of miR-33a is different in intramuscular fat (IMF) tissues from steers and bulls. In the present study, miR-33a was overexpressed in bovine preadipocytes, and a total of 781 differentialy expressed genes were found, including 348 upregulated and 433 downregulated genes. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed genes enriched cell division and cell cycle respectively. MiR-33a overexpression decreased the rate of preadipocyte proliferation. Synchronously, the mRNA and protein expression levels of proliferation-related marker genes, including cyclin B1 (CCNB1) and proliferating cell nuclear antigen (PCNA), were decreased. In contrast, inhibiting miR-33a increased the rate of preadipocyte proliferation, and expression levels of CCNB1 and PCNA. Furthermore, based on luciferase reporter assays, miR-33a targeted directly cyclin-dependent kinase 6 (CDK6)-3'UTR and inhibited CDK6 protein expression. Interestingly, the silencing of CDK6 inhibited bovine preadipocyte proliferation and proliferation-related genes. Therefore, miR-33a inhibits the proliferation of bovine preadipocytes. CDK6 is the target gene of miR-33a and may be involved in the effects of miR-33a on bovine preadipocyte proliferation.

Extracellular vesicles (EVs) are specific subcellular vesicles released by cells under various environmental conditions. Tumescent liposuction is a commonly used procedure in plastic surgery practice. In the present study, we aimed to extract EVs derived from lipoaspirate fluid (LF-EVs) and characterize them using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. The global profiles of proteins and microRNAs from LF-EVs were identified, strongly suggesting a potential regulatory function of LF-EVs. In addition, we investigated the effects and mechanisms of LF-EVs on fat graft survival. Cell functional tests showed that LF-EVs promoted the proliferation, migration, and tube structure formation of human umbilical vein endothelial cells. LF-EVs also promoted the adipogenic differentiation of adipose tissue-derived stem cells. The results of animal experiments showed that the average weights of fat grafts in the LF-EVs-treated group were significantly higher than those in the control group. Histologically, there was less fibrosis, fewer cysts, and increased fat tissue survival in the LF-EVs group. Further investigations of angiogenic and adipogenic factors revealed that LF-EVs also promoted angiogenesis and exerted a pro-adipogenic effect in vivo. Our findings will help to elucidate the functions of LF-EVs and provide a reference dataset for future translational studies.

Vascular diseases such as atherosclerosis and aneurysms are associated with diet. Perivascular adipose tissue (PVAT) was reportedly involved in the regulation of vascular functions. It is suggested that imbalanced diets can cause PVAT inflammation and dysfunction as well as impaired vascular function. However, the association between diets and PVAT are not clearly understood. Here, we showed that a high-fat and a high-sucrose diet affected PVAT at different sites. A high-fat diet induced increased number of large-sized lipid droplets and increased CD (Cluster of differentiation) 68+ macrophage- and monocyte chemotactic protein (MCP)-1-positive areas in the abdominal aortic PVAT (aPVAT). In addition, a high-fat diet caused decreased collagen fibre-positive area and increased CD68+ macrophage- and MCP-1-positive areas in the abdominal aorta. In contrast, a high-sucrose diet induced increased number of large-sized lipid droplets, increased CD68+ macrophage- and MCP-1-positive areas, and decreased UCP-1 positive area in the thoracic aortic PVAT (tPVAT). A high-sucrose diet caused decreased collagen fibre-positive area and increased CD68+ macrophage- and MCP-1-positive areas in the thoracic aorta. These results could be attributed to the different adipocyte populations in the tPVAT and aPVAT. Our results provide pathological evidence to improve our understanding of the relationship between diet and vascular diseases.