Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2123097
Na Li, Yunfei Chen, Haiyan Wang, Jing Li, Robert Chunhua Zhao
Obesity is a chronic metabolic disorder characterized by the accumulation of excess fat in the body. Preventing and controlling obesity by inhibiting the adipogenic differentiation of mesenchymal stem cells (MSCs) and thereby avoiding the increase of white adipose tissue is safe and effective. Recent studies have demonstrated that Sprouty proteins (SPRYs) are involved in cell differentiation and related diseases. However, the role and mechanism of SPRY4 in MSC adipogenic differentiation remain to be explored. Here, we found that SPRY4 positively correlates with the adipogenic differentiation of human adipose-derived MSCs (hAMSCs). Via gain- and loss-of-function experiments, we demonstrated that SPRY4 promotes hAMSC adipogenesis both in vitro and in vivo. Mechanistically, SPRY4 functioned by activating the MEK-ERK1/2 pathway. Our findings provide new insights into a critical role for SPRY4 as a regulator of adipogenic differentiation, which may illuminate the underlying mechanisms of obesity and suggest the potential of SPRY4 as a novel treatment option.
{"title":"SPRY4 promotes adipogenic differentiation of human mesenchymal stem cells through the MEK-ERK1/2 signaling pathway.","authors":"Na Li, Yunfei Chen, Haiyan Wang, Jing Li, Robert Chunhua Zhao","doi":"10.1080/21623945.2022.2123097","DOIUrl":"https://doi.org/10.1080/21623945.2022.2123097","url":null,"abstract":"<p><p>Obesity is a chronic metabolic disorder characterized by the accumulation of excess fat in the body. Preventing and controlling obesity by inhibiting the adipogenic differentiation of mesenchymal stem cells (MSCs) and thereby avoiding the increase of white adipose tissue is safe and effective. Recent studies have demonstrated that Sprouty proteins (SPRYs) are involved in cell differentiation and related diseases. However, the role and mechanism of SPRY4 in MSC adipogenic differentiation remain to be explored. Here, we found that SPRY4 positively correlates with the adipogenic differentiation of human adipose-derived MSCs (hAMSCs). Via gain- and loss-of-function experiments, we demonstrated that SPRY4 promotes hAMSC adipogenesis both in vitro and in vivo. Mechanistically, SPRY4 functioned by activating the MEK-ERK1/2 pathway. Our findings provide new insights into a critical role for SPRY4 as a regulator of adipogenic differentiation, which may illuminate the underlying mechanisms of obesity and suggest the potential of SPRY4 as a novel treatment option.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"588-600"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10617640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The organoid is a 3D cell architecture formed by self-organized tissues or cells in vitro with similar cell types, histological structures, and biological functions of the native organ. Depending on the unique organ structures and cell types, producing organoids requires individualized design and is still challenging. Organoids of some tissues, including adipose tissue, remain to generate to be more faithful to their original organ in structure and function. We previously established a new model of the origin of adipose cells originating from non-adipose fascia tissue. Here, we investigated superficial fascia fragments in 3D hydrogel and found they were able to transform into relatively large adipocyte aggregates containing mature unilocular adipocytes, which were virtually "fat organoids". Such fascia-originated fat organoids had a typical structure of adipose tissues and possessed the principal function of adipose cells in the synthesis, storage, hydrolysis of triglycerides and adipokines secretion. Producing fat organoids from superficial fascia can provide a new approach for adipocyte research and strongly evidences that both adipose tissues and cells originate from fascia. Our findings give insights into metabolic regulation by the crosstalk between different organs and tissues and provide new knowledge for investigating novel treatments for obesity, diabetes and other metabolic diseases.Abbreviations: 3D: three dimensional; ASC: adipose-derived stromal cells; C/EBP: CCAAT-enhancer-binding protein; EdU: 5-ethynyl-2-deoxyuridine; FABP4: fatty acid-binding protein 4; FAS: fatty acid synthase; FSCs: fascia-derived stromal cells; Plin1: perilipin-1; Plin2: perilipin-2; PPARγ: peroxisome proliferator-activated receptor γ; WAT: white adipose tissue.
{"title":"Generation of functional fat organoid from rat superficial fascia.","authors":"Yanfei Zhang, Yuanyuan Zhang, Yingyue Dong, Tongsheng Chen, Guoheng Xu","doi":"10.1080/21623945.2022.2072446","DOIUrl":"https://doi.org/10.1080/21623945.2022.2072446","url":null,"abstract":"<p><p>The organoid is a 3D cell architecture formed by self-organized tissues or cells in vitro with similar cell types, histological structures, and biological functions of the native organ. Depending on the unique organ structures and cell types, producing organoids requires individualized design and is still challenging. Organoids of some tissues, including adipose tissue, remain to generate to be more faithful to their original organ in structure and function. We previously established a new model of the origin of adipose cells originating from non-adipose fascia tissue. Here, we investigated superficial fascia fragments in 3D hydrogel and found they were able to transform into relatively large adipocyte aggregates containing mature unilocular adipocytes, which were virtually \"fat organoids\". Such fascia-originated fat organoids had a typical structure of adipose tissues and possessed the principal function of adipose cells in the synthesis, storage, hydrolysis of triglycerides and adipokines secretion. Producing fat organoids from superficial fascia can provide a new approach for adipocyte research and strongly evidences that both adipose tissues and cells originate from fascia. Our findings give insights into metabolic regulation by the crosstalk between different organs and tissues and provide new knowledge for investigating novel treatments for obesity, diabetes and other metabolic diseases.<b>Abbreviations</b>: 3D: three dimensional; ASC: adipose-derived stromal cells; C/EBP: CCAAT-enhancer-binding protein; EdU: 5-ethynyl-2-deoxyuridine; FABP4: fatty acid-binding protein 4; FAS: fatty acid synthase; FSCs: fascia-derived stromal cells; Plin1: perilipin-1; Plin2: perilipin-2; PPARγ: peroxisome proliferator-activated receptor γ; WAT: white adipose tissue.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"287-300"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10347455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-09DOI: 10.1080/21623945.2022.2073804
Zhijuan Ge, Y. Shang, Wen-die Wang, Ji-gang Yang, Shu-zhen Chen
ABSTRACT Neuroblastoma (NB) is an embryonic malignant tumour of the sympathetic nervous system, and current research shows that activation of brown adipose tissue accelerates cachexia in cancer patients. However, the interaction between brown adipose tissues and NB remains unclear. The study aimed to investigate the effect of brown adipocytes in the co-culture system on the proliferation and migration of NB cells. Brown adipocytes promoted the proliferation and migration of Neuro-2a, BE(2)-M17, and SH-SY5Y cells under the co-culture system, with an increase of the mRNA and protein levels of UCP2 and PPAR-γ in NB cells. The UCP2 inhibitor genipin or PPAR-γ inhibitor T0090709 inhibited the migration of NB cells induced by brown adipocytes. Genipin or siUCP2 upregulated the expression of E-cadherin, and downregulated the expression of N-cadherin and vimentin in NB cells. We suggest that under co-cultivation conditions, NB cells can activate brown adipocytes, which triggers changes in various genes and promotes the proliferation and migration of NB cells. The PPAR-γ/UCP2 pathway is involved in the migration of NB cells caused by brown adipocytes.
{"title":"Brown adipocytes promote epithelial mesenchymal transition of neuroblastoma cells by inducing PPAR-γ/UCP2 expression","authors":"Zhijuan Ge, Y. Shang, Wen-die Wang, Ji-gang Yang, Shu-zhen Chen","doi":"10.1080/21623945.2022.2073804","DOIUrl":"https://doi.org/10.1080/21623945.2022.2073804","url":null,"abstract":"ABSTRACT Neuroblastoma (NB) is an embryonic malignant tumour of the sympathetic nervous system, and current research shows that activation of brown adipose tissue accelerates cachexia in cancer patients. However, the interaction between brown adipose tissues and NB remains unclear. The study aimed to investigate the effect of brown adipocytes in the co-culture system on the proliferation and migration of NB cells. Brown adipocytes promoted the proliferation and migration of Neuro-2a, BE(2)-M17, and SH-SY5Y cells under the co-culture system, with an increase of the mRNA and protein levels of UCP2 and PPAR-γ in NB cells. The UCP2 inhibitor genipin or PPAR-γ inhibitor T0090709 inhibited the migration of NB cells induced by brown adipocytes. Genipin or siUCP2 upregulated the expression of E-cadherin, and downregulated the expression of N-cadherin and vimentin in NB cells. We suggest that under co-cultivation conditions, NB cells can activate brown adipocytes, which triggers changes in various genes and promotes the proliferation and migration of NB cells. The PPAR-γ/UCP2 pathway is involved in the migration of NB cells caused by brown adipocytes.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"335 - 345"},"PeriodicalIF":3.3,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47577183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-09DOI: 10.1080/21623945.2022.2075129
P. V. van Krieken, J. Roos, P. Fischer-Posovszky, S. Wueest, D. Konrad
ABSTRACT Oncostatin M (OSM) is a member of the glycoprotein 130 cytokine family that is involved in chronic inflammation and increased in adipose tissue under obesity and insulin resistance. OSM was shown to inhibit adipogenesis, suppress browning, and contribute to insulin resistance in cultured white adipocytes. In contrast, OSM may have a metabolically favourable role on adipocytes in mouse models of obesity and insulin resistance. However, a putative role of OSM in modulating lipolysis has not been investigated in detail to date. To address this, cultured white adipocytes of mouse or human origin were exposed to 10 or 100 ng/ml of OSM for various time periods. In murine 3T3-L1 cells, OSM stimulation directly activated hormone-sensitive lipase (HSL) and other players of the lipolytic machinery, and dose-dependently increased free fatty acid and glycerol release. In parallel, OSM attenuated insulin-mediated suppression of lipolysis and induced phosphorylation of serine-residues on the insulin receptor substrate-1 (IRS1) protein. Key experiments were verified in a second murine and a human adipocyte cell line. Inhibiton of extracellular signal-regulated kinase (ERK)-1/2 activation, abolished OSM-mediated HSL phosphorylation and lipolysis. In conclusion, OSM signalling directly promotes lipolysis in white adipocytes in an ERK1/2-dependent manner.
肿瘤抑制素M (Oncostatin M, OSM)是糖蛋白130细胞因子家族的一员，参与肥胖和胰岛素抵抗下脂肪组织的慢性炎症和增加。在培养的白色脂肪细胞中，OSM被证明可以抑制脂肪生成，抑制褐变，并有助于胰岛素抵抗。相反，OSM可能对肥胖和胰岛素抵抗小鼠模型中的脂肪细胞具有代谢有利作用。然而，迄今为止，OSM在调节脂肪分解中的假定作用尚未得到详细的研究。为了解决这个问题，将培养的小鼠或人类白色脂肪细胞暴露于10或100 ng/ml的OSM中不同时间。在小鼠3T3-L1细胞中，OSM刺激直接激活激素敏感脂肪酶(HSL)和其他脂溶机制，并剂量依赖性地增加游离脂肪酸和甘油的释放。同时，OSM减弱胰岛素介导的脂肪分解抑制和诱导胰岛素受体底物-1 (IRS1)蛋白丝氨酸残基磷酸化。在第二种小鼠和人类脂肪细胞系中验证了关键实验。抑制细胞外信号调节激酶(ERK)-1/2的激活，消除osm介导的HSL磷酸化和脂肪分解。综上所述，OSM信号以erk1 /2依赖的方式直接促进白色脂肪细胞的脂肪分解。
{"title":"Oncostatin M promotes lipolysis in white adipocytes","authors":"P. V. van Krieken, J. Roos, P. Fischer-Posovszky, S. Wueest, D. Konrad","doi":"10.1080/21623945.2022.2075129","DOIUrl":"https://doi.org/10.1080/21623945.2022.2075129","url":null,"abstract":"ABSTRACT Oncostatin M (OSM) is a member of the glycoprotein 130 cytokine family that is involved in chronic inflammation and increased in adipose tissue under obesity and insulin resistance. OSM was shown to inhibit adipogenesis, suppress browning, and contribute to insulin resistance in cultured white adipocytes. In contrast, OSM may have a metabolically favourable role on adipocytes in mouse models of obesity and insulin resistance. However, a putative role of OSM in modulating lipolysis has not been investigated in detail to date. To address this, cultured white adipocytes of mouse or human origin were exposed to 10 or 100 ng/ml of OSM for various time periods. In murine 3T3-L1 cells, OSM stimulation directly activated hormone-sensitive lipase (HSL) and other players of the lipolytic machinery, and dose-dependently increased free fatty acid and glycerol release. In parallel, OSM attenuated insulin-mediated suppression of lipolysis and induced phosphorylation of serine-residues on the insulin receptor substrate-1 (IRS1) protein. Key experiments were verified in a second murine and a human adipocyte cell line. Inhibiton of extracellular signal-regulated kinase (ERK)-1/2 activation, abolished OSM-mediated HSL phosphorylation and lipolysis. In conclusion, OSM signalling directly promotes lipolysis in white adipocytes in an ERK1/2-dependent manner.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"315 - 324"},"PeriodicalIF":3.3,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42158852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ABSTRACT Obesity is emerging as an epidemiological issue, being associated with the onset and progress of various metabolism-related disorders. Obesity is characterized by the white adipose expansion, which encounters white adipocyte hypertrophy and hyperplasia. White adipocyte hyperplasia is defined as adipogenesis with the increase in the number of the white adipocytes from the preadipocytes. Adipogenesis contributes to distributing excess triglycerides among the smaller newly formed adipocytes, reducing the number of hypertrophic adipocytes and secreting anti-inflammatory factor. Therefore, adipogenesis is emerging as a new therapeutic target for the treatment of obesity. In the present study, for a better understanding of the contribution of the alteration of the omental differentiated white adipocytes to the systemic metabolic disorders, we downloaded the mRNA expression profiles from GEO database GSE1657, 328 differentially expressed genes (DEGs) were screened between the undifferentiated preadipocytes (UNDIF) and omental differentiated white adipocytes (DIF). The contributions of the upregulated and downregulated DEGs to the system were performed via the Gene Ontology (GO) analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein–Protein Interaction (PPI) network, respectively. The potential contribution of the whole altered genes in the differentiated white adipocytes was explored with the performance of Gene Set Enrichment Analysis (GSEA), especially on the GO analysis, KEGG analysis, hallmark analysis, oncogenic analysis and related miRNA analysis. The output of the current study will shed light on the new targets for the treatment of obesity and obesity-related disorders.
肥胖正在成为一个流行病学问题，与各种代谢相关疾病的发生和进展有关。肥胖的特征是白色脂肪扩张，同时伴随着白色脂肪细胞的肥大和增生。白色脂肪细胞增生被定义为脂肪形成，白色脂肪细胞的数量从前脂肪细胞增加。脂肪生成有助于将多余的甘油三酯分布在较小的新形成的脂肪细胞中，减少肥厚脂肪细胞的数量并分泌抗炎因子。因此，脂肪生成正在成为治疗肥胖的一个新的治疗靶点。在本研究中，为了更好地了解网膜分化白色脂肪细胞的改变对全身性代谢紊乱的贡献，我们从GEO数据库GSE1657下载了mRNA表达谱，在未分化前脂肪细胞(UNDIF)和网膜分化白色脂肪细胞(DIF)之间筛选了328个差异表达基因(deg)。通过基因本体(GO)分析、京都基因与基因组百科全书(KEGG)途径分析和蛋白质-蛋白质相互作用(PPI)网络，分别对上调和下调的deg对系统的贡献进行了分析。通过基因集富集分析(Gene Set Enrichment Analysis, GSEA)，特别是GO分析、KEGG分析、hallmark分析、致癌分析和相关miRNA分析，探讨了整个改变基因在分化的白色脂肪细胞中的潜在贡献。目前的研究成果将为肥胖和肥胖相关疾病的治疗提供新的目标。
{"title":"Analysis of the different characteristics between omental preadipocytes and differentiated white adipocytes using bioinformatics methods","authors":"Xinyu Yang, Lu Li, Canming Xu, Meichen Pi, Changhua Wang, Yemin Zhang","doi":"10.1080/21623945.2022.2063471","DOIUrl":"https://doi.org/10.1080/21623945.2022.2063471","url":null,"abstract":"ABSTRACT Obesity is emerging as an epidemiological issue, being associated with the onset and progress of various metabolism-related disorders. Obesity is characterized by the white adipose expansion, which encounters white adipocyte hypertrophy and hyperplasia. White adipocyte hyperplasia is defined as adipogenesis with the increase in the number of the white adipocytes from the preadipocytes. Adipogenesis contributes to distributing excess triglycerides among the smaller newly formed adipocytes, reducing the number of hypertrophic adipocytes and secreting anti-inflammatory factor. Therefore, adipogenesis is emerging as a new therapeutic target for the treatment of obesity. In the present study, for a better understanding of the contribution of the alteration of the omental differentiated white adipocytes to the systemic metabolic disorders, we downloaded the mRNA expression profiles from GEO database GSE1657, 328 differentially expressed genes (DEGs) were screened between the undifferentiated preadipocytes (UNDIF) and omental differentiated white adipocytes (DIF). The contributions of the upregulated and downregulated DEGs to the system were performed via the Gene Ontology (GO) analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein–Protein Interaction (PPI) network, respectively. The potential contribution of the whole altered genes in the differentiated white adipocytes was explored with the performance of Gene Set Enrichment Analysis (GSEA), especially on the GO analysis, KEGG analysis, hallmark analysis, oncogenic analysis and related miRNA analysis. The output of the current study will shed light on the new targets for the treatment of obesity and obesity-related disorders.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"227 - 238"},"PeriodicalIF":3.3,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46133356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-28DOI: 10.1080/21623945.2022.2069311
Lusha Li, Liangli Chen, Li Yu, Junlu Zhang, Liying Chen
ABSTRACT We explored potential biomarkers and molecular mechanisms regarding breast cancer (BC) risk reduction after intermittent energy restriction (IER) and further explored the association between IER and BC prognosis. We identified differentially expressed genes (DEGs) in breast tissues before and after IER by analyzing the expression profile from GEO. Then, enrichment analysis was used to identify important pathways of DEGs and hub genes were selected from PPI network. After that, GEPIA, ROC, and KM plotter were used to explore the preventive and prognostic value of hub genes. It was found that FOXM1 and CXCR4 were highly expressed in BC tissues and associated with the worse prognosis. FOXM1 and CXCR4 were down-regulated after IER , which meant that FOXM1 and CXCR4 might be the most important key genes for reducing the risk and improving prognosis of BC after IER . ROC curve indicated that FOXM1 and CXCR4 also had the predictive value for BC. Our study contributed to a better understanding of the specific mechanisms in protective effects of IER on BC and provided a new approach to improve the prognosis of BC, which might provide partial guidance for the subsequent development of more effective treatments and prevention strategies.
{"title":"Identification of FOXM1 and CXCR4 as key genes in breast cancer prevention and prognosis after intermittent energy restriction through bioinformatics and functional analyses","authors":"Lusha Li, Liangli Chen, Li Yu, Junlu Zhang, Liying Chen","doi":"10.1080/21623945.2022.2069311","DOIUrl":"https://doi.org/10.1080/21623945.2022.2069311","url":null,"abstract":"ABSTRACT We explored potential biomarkers and molecular mechanisms regarding breast cancer (BC) risk reduction after intermittent energy restriction (IER) and further explored the association between IER and BC prognosis. We identified differentially expressed genes (DEGs) in breast tissues before and after IER by analyzing the expression profile from GEO. Then, enrichment analysis was used to identify important pathways of DEGs and hub genes were selected from PPI network. After that, GEPIA, ROC, and KM plotter were used to explore the preventive and prognostic value of hub genes. It was found that FOXM1 and CXCR4 were highly expressed in BC tissues and associated with the worse prognosis. FOXM1 and CXCR4 were down-regulated after IER , which meant that FOXM1 and CXCR4 might be the most important key genes for reducing the risk and improving prognosis of BC after IER . ROC curve indicated that FOXM1 and CXCR4 also had the predictive value for BC. Our study contributed to a better understanding of the specific mechanisms in protective effects of IER on BC and provided a new approach to improve the prognosis of BC, which might provide partial guidance for the subsequent development of more effective treatments and prevention strategies.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"301 - 314"},"PeriodicalIF":3.3,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46080002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-17DOI: 10.1080/21623945.2022.2063015
Sen Li, Xiaolin Zong, Liheng Zhang, Luya Li, Jianxin Wu
ABSTRACT Obesity has become a serious global public health problem; a deeper understanding of systemic change of chromatin accessibility during human adipogenesis contributes to conquering obesity and its related diseases. Here, we applied the ATAC-seq method to depict a high-quality genome‐wide time-resolved accessible chromatin atlas during adipogenesis of human adipose-derived stem cells (hASCs). Our data indicated that the chromatin accessibility drastic dynamically reformed during the adipogenesis of hASCs and 8 h may be the critical transition node of adipogenesis chromatin states from commitment phase to determination phase. Moreover, upon adipogenesis, we also found that the chromatin accessibility of regions related to anti-apoptotic, angiogenic and immunoregulatory gradually increased, which is beneficial to maintaining the health of adipose tissue (AT). Finally, the chromatin accessibility changed significantly in intronic regions of peroxisome proliferator‐activated receptor γ during adipogenesis, and these regions were rich in transcription factors binding motifs that were exposed for further regulation. Overall, we systematically analysed the complex change of chromatin accessibility occurring in the early stage of adipogenesis and deepened our understanding of human adipogenesis. Furthermore, we also provided a good reference data resource of genome‐wide chromatin accessibility for future studies on human adipogenesis.
{"title":"A chromatin accessibility landscape during early adipogenesis of human adipose-derived stem cells","authors":"Sen Li, Xiaolin Zong, Liheng Zhang, Luya Li, Jianxin Wu","doi":"10.1080/21623945.2022.2063015","DOIUrl":"https://doi.org/10.1080/21623945.2022.2063015","url":null,"abstract":"ABSTRACT Obesity has become a serious global public health problem; a deeper understanding of systemic change of chromatin accessibility during human adipogenesis contributes to conquering obesity and its related diseases. Here, we applied the ATAC-seq method to depict a high-quality genome‐wide time-resolved accessible chromatin atlas during adipogenesis of human adipose-derived stem cells (hASCs). Our data indicated that the chromatin accessibility drastic dynamically reformed during the adipogenesis of hASCs and 8 h may be the critical transition node of adipogenesis chromatin states from commitment phase to determination phase. Moreover, upon adipogenesis, we also found that the chromatin accessibility of regions related to anti-apoptotic, angiogenic and immunoregulatory gradually increased, which is beneficial to maintaining the health of adipose tissue (AT). Finally, the chromatin accessibility changed significantly in intronic regions of peroxisome proliferator‐activated receptor γ during adipogenesis, and these regions were rich in transcription factors binding motifs that were exposed for further regulation. Overall, we systematically analysed the complex change of chromatin accessibility occurring in the early stage of adipogenesis and deepened our understanding of human adipogenesis. Furthermore, we also provided a good reference data resource of genome‐wide chromatin accessibility for future studies on human adipogenesis.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"239 - 249"},"PeriodicalIF":3.3,"publicationDate":"2022-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45442723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1080/21623945.2022.2062852
Jie Pan, S. Kothan, Aye Thidar Moe Moe, Kun Huang
ABSTRACT The mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin signaling, respectively. Level of phosphoinositide-3-kinase (PI3K) after induction of beige adipocytes under conditions of normal insulin signaling, phosphorylated protein kinase B (pAKT), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), zinc-fifinger transcriptional factor PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPβ) were significantly increased. Conversely, when insulin signaling is incompletely inhibited, the expression of the thermogenic and adipogenic factors is significantly reduced, with obvious impairment of adipogenesis. However, phosphorylation level of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and expression level of sirtuin type 1 (SIRT1) had increased. These white preadipocytes from different donors showed similar dynamic change in morphology and molecular levels during the browning. The present data indicate that insulin signaling plays a important role in regulation of browning of hsASCs and msASCs through PI3K-AKT-UCP1 signaling pathway. The insulin-AMPK-SIRT1 pathway was also involved in the adipocytes browning, while its effect is limited.
{"title":"Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes","authors":"Jie Pan, S. Kothan, Aye Thidar Moe Moe, Kun Huang","doi":"10.1080/21623945.2022.2062852","DOIUrl":"https://doi.org/10.1080/21623945.2022.2062852","url":null,"abstract":"ABSTRACT The mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin signaling, respectively. Level of phosphoinositide-3-kinase (PI3K) after induction of beige adipocytes under conditions of normal insulin signaling, phosphorylated protein kinase B (pAKT), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), zinc-fifinger transcriptional factor PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPβ) were significantly increased. Conversely, when insulin signaling is incompletely inhibited, the expression of the thermogenic and adipogenic factors is significantly reduced, with obvious impairment of adipogenesis. However, phosphorylation level of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and expression level of sirtuin type 1 (SIRT1) had increased. These white preadipocytes from different donors showed similar dynamic change in morphology and molecular levels during the browning. The present data indicate that insulin signaling plays a important role in regulation of browning of hsASCs and msASCs through PI3K-AKT-UCP1 signaling pathway. The insulin-AMPK-SIRT1 pathway was also involved in the adipocytes browning, while its effect is limited.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"213 - 226"},"PeriodicalIF":3.3,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49647668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-12DOI: 10.1080/21623945.2022.2060059
Kemin Yan, Pengyuan Zhang, Jiewen Jin, Xin Chen, H. Guan, Yanbing Li, Hai Li
ABSTRACT Bariatric surgery (BS) is an effective treatment for obesity. Adipose tissue, liver tissue and skeletal muscle are important metabolic tissues. This study investigated hub genes and their association with immune infiltration in these metabolic tissues of obese patients after BS by bioinformatic analysis with Gene Expression Omnibus datasets. Differentially expressed genes (DEGs) were identified, and a protein–protein interaction network was constructed to identify hub genes. As a result, 121 common DEGs were identified and mainly enriched in cytokine–cytokine receptor interactions, chemokine signaling pathway, neutrophil activation and immune responses. Immune cell infiltration analysis showed that the abundance of M1 macrophages was significantly lower in adipose and liver tissue after BS (p<0.05). Ten hub genes (TYROBP, TLR8, FGR, NCF2, HCK, CCL2, LAPTM5, MNDA and S100A9) that were all downregulated after BS were also associated with immune cells. Consistently, results in the validated dataset showed that the expression levels of these hub genes were increased in obese patients and mice, and decreased after BS. In conclusion, this study analysed the potential immune and inflammatory mechanisms of BS in three key metabolic tissues of obese patients, and revealed hub genes associated with immune cell infiltration, thus providing potential targets for obesity treatment.
{"title":"Integrative analyses of hub genes and their association with immune infiltration in adipose tissue, liver tissue and skeletal muscle of obese patients after bariatric surgery","authors":"Kemin Yan, Pengyuan Zhang, Jiewen Jin, Xin Chen, H. Guan, Yanbing Li, Hai Li","doi":"10.1080/21623945.2022.2060059","DOIUrl":"https://doi.org/10.1080/21623945.2022.2060059","url":null,"abstract":"ABSTRACT Bariatric surgery (BS) is an effective treatment for obesity. Adipose tissue, liver tissue and skeletal muscle are important metabolic tissues. This study investigated hub genes and their association with immune infiltration in these metabolic tissues of obese patients after BS by bioinformatic analysis with Gene Expression Omnibus datasets. Differentially expressed genes (DEGs) were identified, and a protein–protein interaction network was constructed to identify hub genes. As a result, 121 common DEGs were identified and mainly enriched in cytokine–cytokine receptor interactions, chemokine signaling pathway, neutrophil activation and immune responses. Immune cell infiltration analysis showed that the abundance of M1 macrophages was significantly lower in adipose and liver tissue after BS (p<0.05). Ten hub genes (TYROBP, TLR8, FGR, NCF2, HCK, CCL2, LAPTM5, MNDA and S100A9) that were all downregulated after BS were also associated with immune cells. Consistently, results in the validated dataset showed that the expression levels of these hub genes were increased in obese patients and mice, and decreased after BS. In conclusion, this study analysed the potential immune and inflammatory mechanisms of BS in three key metabolic tissues of obese patients, and revealed hub genes associated with immune cell infiltration, thus providing potential targets for obesity treatment.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"190 - 201"},"PeriodicalIF":3.3,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42859139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-11DOI: 10.1080/21623945.2022.2064956
Jie Ren, Hui Zhang, Jinna Wang, Yi-yi Xu, Lei Zhao, Q. Yuan
ABSTRACT Lung adenocarcinoma (LUAD) is amongst the major contributors to cancer-related deaths on a global scale. Adipocytokines and long non-coding RNAs (lncRNAs) are indispensable participants in cancer. We performed a pan-cancer analysis of the mRNA expression, single nucleotide variation, copy number variation, and prognostic value of adipocytokines. LUAD samples were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Simultaneously, train, internal and external cohorts were grouped. After a stepwise screening of optimized genes through least absolute shrinkage and selection operator regression analysis, random forest algorithm,, and Cox regression analysis, an adipocytokine-related prognostic signature (ARPS) with superior performance compared with four additional well-established signatures for survival prediction was constructed. After determination of risk levels, the discrepancy of immune microenvironment, immune checkpoint gene expression, immune subtypes, and immune response in low- and high-risk cohorts were explored through multiple bioinformatics methods. Abnormal pathways underlying high- and low-risk subgroups were identified through gene set enrichment analysis (GSEA). Immune-and metabolism-related pathways that were correlated with risk score were selected through single sample GSEA. Finally, a nomogram with satisfied predictive survival probability was plotted. In summary, this study offers meaningful information for clinical treatment and scientific investigation.
肺腺癌(LUAD)是全球范围内导致癌症相关死亡的主要原因之一。脂肪细胞因子和长链非编码rna (lncRNAs)是癌症发生过程中不可或缺的参与者。我们对脂肪细胞因子的mRNA表达、单核苷酸变异、拷贝数变异和预后价值进行了泛癌分析。LUAD样本来自Gene Expression Omnibus (GEO)和the Cancer Genome Atlas (TCGA)数据库。同时，对培训、内部和外部队列进行分组。通过最小绝对收缩和选择算子回归分析、随机森林算法和Cox回归分析逐步筛选优化基因后，构建了一个与其他四个已建立的生存预测特征相比性能优越的脂肪细胞因子相关预后特征(ARPS)。在确定风险水平后，通过多种生物信息学方法探讨低、高危人群免疫微环境、免疫检查点基因表达、免疫亚型和免疫应答的差异。通过基因集富集分析(GSEA)确定了高风险和低风险亚组的异常途径。通过单样本GSEA选择与风险评分相关的免疫和代谢相关途径。最后，绘制具有满意预测生存概率的nomogram。本研究为临床治疗和科学研究提供了有意义的信息。
{"title":"Transcriptome analysis of adipocytokines and their-related LncRNAs in lung adenocarcinoma revealing the association with prognosis, immune infiltration, and metabolic characteristics","authors":"Jie Ren, Hui Zhang, Jinna Wang, Yi-yi Xu, Lei Zhao, Q. Yuan","doi":"10.1080/21623945.2022.2064956","DOIUrl":"https://doi.org/10.1080/21623945.2022.2064956","url":null,"abstract":"ABSTRACT Lung adenocarcinoma (LUAD) is amongst the major contributors to cancer-related deaths on a global scale. Adipocytokines and long non-coding RNAs (lncRNAs) are indispensable participants in cancer. We performed a pan-cancer analysis of the mRNA expression, single nucleotide variation, copy number variation, and prognostic value of adipocytokines. LUAD samples were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Simultaneously, train, internal and external cohorts were grouped. After a stepwise screening of optimized genes through least absolute shrinkage and selection operator regression analysis, random forest algorithm,, and Cox regression analysis, an adipocytokine-related prognostic signature (ARPS) with superior performance compared with four additional well-established signatures for survival prediction was constructed. After determination of risk levels, the discrepancy of immune microenvironment, immune checkpoint gene expression, immune subtypes, and immune response in low- and high-risk cohorts were explored through multiple bioinformatics methods. Abnormal pathways underlying high- and low-risk subgroups were identified through gene set enrichment analysis (GSEA). Immune-and metabolism-related pathways that were correlated with risk score were selected through single sample GSEA. Finally, a nomogram with satisfied predictive survival probability was plotted. In summary, this study offers meaningful information for clinical treatment and scientific investigation.","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"11 1","pages":"250 - 265"},"PeriodicalIF":3.3,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48589135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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