Adipocyte最新文献

The objective of this study was to identify key secretory protein-encoding differentially expressed genes (SP-DEGs) in adipose tissue in female metabolic syndrome, thus detecting potential targets in treatment. We examined gene expression profiles in 8 women with metabolic syndrome and 7 healthy, normal body weight women. A total of 143 SP-DEGs were screened, including 83 upregulated genes and 60 downregulated genes. GO analyses of these SP-DEGs included proteolysis, angiogenesis, positive regulation of endothelial cell proliferation, immune response, protein processing, positive regulation of neuroblast proliferation, cell adhesion and ER to Golgi vesicle-mediated transport. KEGG pathway analysis of the SP-DEGs were involved in the TGF-beta signalling pathway, cytokine‒cytokine receptor interactions, the hippo signalling pathway, Malaria. Two modules were identified from the PPI network, namely, Module 1 (DNMT1, KDM1A, NCoR1, and E2F1) and Module 2 (IL-7 R, IL-12A, and CSF3). The gene DNMT1 was shared between the network modules and the WGCNA brown module. According to the single-gene GSEA results, DNMT1 was significantly positively correlated with histidine metabolism and phenylalanine metabolism. This study identified 7 key SP-DEGs in adipose tissue. DNMT1 was selected as the central gene in the development of metabolic syndrome and might be a potential therapeutic target.

Obesity is characterized by macrophage infiltration into adipose tissue. White adipose tissue remodelling under inflammatory conditions involves both hypertrophy and adipogenesis and is regulated by transcription factors, which are influenced by bone morphogenetic protein (BMP) signalling. MicroRNAs (miRNAs) regulate gene expression and are involved in obesity-related processes such as adipogenesis. Therefore, we identified differentially expressed miRNAs in the epididymal white adipose tissue (eWAT) of mice fed a normal diet (ND) and those fed a high-fat diet (HFD). The expression of miR-6402 was significantly suppressed in the inflamed eWAT of HFD-fed mice than in ND-fed mice. Furthermore, Bmpr2, the receptor for BMP4, was identified as a target gene of miR-6402. Consistently, miR-6402 was downregulated in the inflamed eWAT of HFD-fed mice and in 3T3-L1 cells (preadipocytes) and differentiated 3T3-L1 cells (mature adipocytes) , and BMPR2 expression in these cells was upregulated. Adipogenesis was induced in WAT by BMP4 injection (in vivo) and in 3T3-L1 cells by BMP4 stimulation (in vitro), both of which were inhibited by miR-6402 transfection. Inflamed eWAT showed higher expression of BMPR2 and the adipogenesis markers C/EBPβ and PPARγ, which was suppressed by miR-6402 transfection. Our findings suggest that miR-6402 is a novel anti-adipogenic miRNA that combats obesity by inhibiting the BMP4/BMPR2 signalling pathway and subsequently reducing adipose tissue expansion.

Immune cell infiltration into adipose tissue (AT) is a key factor in type 2 diabetes (T2DM). However, research on the impact of fat distribution on immune cells and immune responses in women is still lacking. This study used enrichment, protein-protein interaction network, immune cell infiltration, and correlation analysis to compare the similarities and differences between the transcriptome data of visceral AT (VAT) and subcutprotein-proteinaneous AT (SAT) obtained from the omprehensive database of gene expression in women with non-T2DM and T2DM. DEGs with the same biological function in two types of ATs often exhibited different expression trends. SharedVAT-specific and SAT-specific hub genes were mainly associated with transcription factors, monocyte-macrophage markers, and chemokines, respectively. Immune cells affected by both AT types included monocytes, granulocytes, T and B lymphocytes, and NK cells. VAT affected more immune cells, mainly myeloid cells. Shared hub genes in VAT correlated positively with M1 macrophages, suggesting pro-inflammatory effects, while those in SAT correlated negatively with M1 macrophages and lymphocytes, suggesting anti-inflammatory effects. This study provides a theoretical basis for further understanding the correlation between AT and T2DM in women.

Adipocyte hypertrophy is a critical contributor to obesity-induced inflammation and insulin resistance. This study employed a human adipocyte hypertrophy model to investigate the adipokine release, inflammatory responses, and the intracellular singling pathways. Hypertrophic adipocytes exhibited increased lipid content and lipolysis, a decline of anti-inflammatory adipokine adiponectin release and an increase of pro-inflammatory adipokine leptin release compared to mature adipocytes. Moreover, TNFα and LPS exacerbated the decrease in adiponectin secretion by hypertrophic adipocytes while promoting the secretion of leptin, MCP-1 and IL-6, which is associated with impaired activation of p38 and JNK MAPK and persistent activation of ERK and IκBα in hypertrophic adipocytes. These altered adipokine secretions and inflammatory responses within hypertrophic adipocytes may contribute to adipocyte dysfunction in human obesity.

Skin contracts during wound healing to facilitate wound closure. In some patients, skin contraction can lead to the formation of skin contractures that limit movement, impair function, and significantly impact well-being. Current treatment options for skin contractures are burdensome for patients, and there is a high risk of recurrence. Autologous fat grafting can improve the structure and function of scarred skin; however, relatively little is known about the effect of fat on skin contraction. In this study, an in vitro tissue-engineered model of human skin was used to test the effects of adipose tissue and adipose-derived stromal cells on skin contraction. Untreated tissue-engineered skin contracted to approximately 60% of the original area over 14 days in culture. The addition of adipose tissue reduced this contraction by 50%. Adipose tissue, which was emulsified or concentrated and high doses of adipose-derived stromal cells (ADSC) were able to inhibit contraction to a similar degree; however, lower doses of ADSC did not show the same effect. In conclusion, the subcutaneous application of adipose tissue has the potential to inhibit skin contraction. This study provides in vitro evidence to support the use of autologous fat grafting to prevent skin contraction in patients most at risk.

Mesenchymal stem cells (MSCs) serve as ideal candidates for a broad range of cell-based therapies. However, cell ageing caused by long-term in vitro expansion and poor survival after in vivo delivery greatly limits their success in preclinical and clinical applications. Dedifferentiation represents a potential strategy for enhancing the retention and function of MSCs in hostile environments. In this study, we evaluated the cell phenotype, proliferation, and differentiation potential, as well as the anti-oxidative stress ability of human umbilical cord-derived MSCs (hMSCs) manipulated with adipogenic priming and subsequent dedifferentiation. After an in vitro differentiation and dedifferentiation procedure, the resultant dedifferentiated hMSCs (De-hMSCs) displayed properties similar to their original counterparts, including immunophenotype and mesodermal potential. Upon re-induction, De-hMSCs exhibited a significantly higher adipogenic differentiation capability than unmanipulated hMSCs. Importantly, De-hMSCs showed a significantly enhanced ability to resist tert-butyl hydroperoxide (t-BHP) induced apoptosis compared to undifferentiated hMSCs. Mechanisms involving bcl-2 family proteins and autophagy may contribute to the demonstrated advantages of dedifferentiation-reprogrammed hMSCs. These results indicate that adipogenic dedifferentiation promotes adipogenesis and cell persistence, as well as preserves the stemness of human umbilical cord-derived MSCs that have been committed to the adipocytic lineage. As a unique stem cell population, dedifferentiated MSCs may represent an attractive and promising candidate for MSC-based therapy.

Post-translational modification by the small ubiquitin-like modifier (SUMO) is essential for cellular differentiation and homeostasis. Here, we investigate the role of SUMOylation in adipose tissue development using TAK-981, a pharmacological inhibitor of SUMOylation. Administration of TAK-981 to mice resulted in significant defect in weight gain and adipocyte atrophy in perigonadal white adipose tissue (gWAT) depots. Gene expression analyses revealed a marked downregulation of adipogenic genes, including Pparg, Cebpa, and Fasn. Our data thus indicate that TAK-981 treatment impaired adipogenesis in gWAT, consistent with prior findings that SUMOylation supports transcriptional regulation of adipogenesis and lipid metabolism. We also found significant infiltration of immune cells and efferocytosis in gWAT. Our results thus indicate that SUMOylation inhibition using a small molecule phenocopies genetic hypoSUMOylation models, highlighting its critical role in maintaining adipocyte functionality and immune environment. These findings provide evidence that SUMOylation is essential for fat accumulation in vivo. Furthermore, given that TAK-981 is currently under clinical evaluation for the treatment of solid tumors, our results underscore the importance of considering the potential unintended effects of SUMOylation inhibition on adipose tissue in patients.

Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are in vitro experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.

 Phosphatase and tensin homolog (PTEN) hamartoma tumour syndrome (PHTS) is a rare disorder caused by germline mutations in the tumour suppressor gene PTEN, a key negative regulator of phosphatidylinositol 3-kinase (PI3K)/AKT signalling. Children with PHTS often develop lipomas, for which only surgical resection is available as treatment. We investigated the effects of the selective PI3K-inhibitor alpelisib on Pten-deficient lipomas. After incubation with alpelisib or the non-selective PI3K inhibitor wortmannin, we analysed histology, gene expression, and Pi3k pathway in lipoma and control epididymal adipose tissue (epiWAT). Alpelisib increased adipocyte area in lipomas compared to epiWAT. Baseline gene expression showed higher levels of markers for proliferation (Pcna), fibrosis (Tgfb1), and adipogenesis (Pparg) in lipomas, while hormone-sensitive lipase expression was lower than in epiWAT. Following alpelisib incubation, target genes of Pi3k signalling and extracellular matrix factors were reduced. We confirmed Pi3k inhibition through detecting decreased Akt levels compared to control treatment. Human lipoma samples treated with alpelisib showed variable lipolysis responses, suggesting variability in therapeutic outcomes. We established an ex vivo model to study alpelisib effects on Pten-deficient lipomas. These results underscore the therapeutic potential of targeted PI3K inhibition in the treatment of PHTS-associated lipomas, particularly in cases that are inoperable.

Lipid droplets (LDs) are highly specialized energy storage organelles involved in the maintenance of lipid homoeostasis by regulating lipid flux within white adipose tissue (WAT). The physiological function of adipocytes and LDs can be compromised by mutations in several genes, leading to NEFA-induced lipotoxicity, which ultimately manifests as metabolic complications, predominantly in the form of dyslipidemia, ectopic fat accumulation, and insulin resistance. In this review, we delineate the effects of mutations and deficiencies in genes - CIDEC, PPARG, BSCL2, AGPAT2, PLIN1, LIPE, LMNA, CAV1, CEACAM1, and INSR - involved in lipid droplet metabolism and their associated pathophysiological impairments, highlighting their roles in the development of lipodystrophies and metabolic dysfunction.