An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.Th...An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.The precise nature of these regulatory factors and their roles at bridging the bone,bone marrow adipose tissue,extramedullary body fat and whole-body energy homeostasis are being explored.In this study,we report that KIAA1199,a secreted factor produced from bone and bone marrow,previously described as an inhibitor of bone formation,also plays a role at promoting adipogenesis.KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue,subcutaneous and visceral fat tissue mass,blood cholesterol,triglycerides,free fatty acids and glycerol,as well as improved insulin sensitivity in skeletal muscle,liver and fat.Moreover,these mice are protected from the detrimental effects of high-fat diet feeding,with decreased obesity,lower blood glucose and glucose tolerance,as well as decreased adipose tissue inflammation,insulin resistance and hepatic steatosis.In human studies,plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol,triglycerides,free fatty acids,glycerol,fasting glucose and HOMA-IR.Mechanistically,KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT/ERK signaling.These findings provide evidence for the role of bone secreted factors on coupling bone,fat and whole-body energy homeostasis.展开更多
2024年1月,上海交通大学医学院附属瑞金医院胰腺中心—上海市胰腺肿瘤转化研究重点实验室的沈柏用教授团队,在Nature Medicine上发表了题为“Prospective observational study on biomarkers of response in pancreatic ductal adenocar...2024年1月,上海交通大学医学院附属瑞金医院胰腺中心—上海市胰腺肿瘤转化研究重点实验室的沈柏用教授团队,在Nature Medicine上发表了题为“Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma”的研究论文。该团队开展了一项前瞻性观察研究,共纳入了1171例接受根治性切除术的胰腺癌患者。首先,通过显微切割方式获取了191例胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)患者的肿瘤配对样本,并进行了蛋白质组学分析,揭示了胰腺肿瘤的独特蛋白模块,尤其是与化疗药物敏感性相关的模块。进一步,研究团队建立了胰腺癌蛋白质组学水平的预后风险模型,并通过外部队列验证了该预后模型的有效性和可靠性。利用多中心、大样本数据,研究构建并验证了NDUFB8和CEMIP2这2种蛋白标志物在预测胰腺肿瘤化疗效能方面的泛化性。展开更多
基金supports from Odense University Hospital PhD fellowship(2014)the NovoNordisk Foundations(NNF15OC0016284,NNF19OC0057449)+2 种基金the Innovation Foundation of Denmark(5166-00002B)National Natural Science Foundation of China(No.32060155,82260284)Guangxi Medical and Health Key Discipline Construction Project.
文摘An increasing number of studies have characterized the bone as an endocrine organ,and that bone secreted factors may not only regulate local bone remodeling,but also other tissues and whole-body metabolic functions.The precise nature of these regulatory factors and their roles at bridging the bone,bone marrow adipose tissue,extramedullary body fat and whole-body energy homeostasis are being explored.In this study,we report that KIAA1199,a secreted factor produced from bone and bone marrow,previously described as an inhibitor of bone formation,also plays a role at promoting adipogenesis.KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue,subcutaneous and visceral fat tissue mass,blood cholesterol,triglycerides,free fatty acids and glycerol,as well as improved insulin sensitivity in skeletal muscle,liver and fat.Moreover,these mice are protected from the detrimental effects of high-fat diet feeding,with decreased obesity,lower blood glucose and glucose tolerance,as well as decreased adipose tissue inflammation,insulin resistance and hepatic steatosis.In human studies,plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol,triglycerides,free fatty acids,glycerol,fasting glucose and HOMA-IR.Mechanistically,KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT/ERK signaling.These findings provide evidence for the role of bone secreted factors on coupling bone,fat and whole-body energy homeostasis.
文摘2024年1月,上海交通大学医学院附属瑞金医院胰腺中心—上海市胰腺肿瘤转化研究重点实验室的沈柏用教授团队,在Nature Medicine上发表了题为“Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma”的研究论文。该团队开展了一项前瞻性观察研究,共纳入了1171例接受根治性切除术的胰腺癌患者。首先,通过显微切割方式获取了191例胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)患者的肿瘤配对样本,并进行了蛋白质组学分析,揭示了胰腺肿瘤的独特蛋白模块,尤其是与化疗药物敏感性相关的模块。进一步,研究团队建立了胰腺癌蛋白质组学水平的预后风险模型,并通过外部队列验证了该预后模型的有效性和可靠性。利用多中心、大样本数据,研究构建并验证了NDUFB8和CEMIP2这2种蛋白标志物在预测胰腺肿瘤化疗效能方面的泛化性。
