Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in th...Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in the pathogenesis of the disease and its progression towards heart failure,including endothelial dysfunction,autonomic neuropathy,metabolic alterations,oxidative stress,and alterations in ion homeostasis,especially calcium transients[1].In Military Medical Research,Jiang et al.[2]sought to determine the functional role of complement factor D(Adipsin)in the pathophysiology of diabetic cardiomyopathy.展开更多
基金National Institutes of Health(NIH):National Heart,Lung,and Blood Institute(NHLBI:R01-HL164772,R01-HL159062,R01-HL146691,T32-HL144456)National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK:R01-DK123259,R01-DK033823)+2 种基金National Center for Advancing Translational Sciences(NCATS:UL1-TR002556-06,UM1-TR004400)(to Gaetano Santulli)Diabetes Action Research and Education Foundation(to Gaetano Santulli)Monique Weill-Caulier and Irma T.Hirschl Trusts(to Gaetano Santulli).
文摘Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in the pathogenesis of the disease and its progression towards heart failure,including endothelial dysfunction,autonomic neuropathy,metabolic alterations,oxidative stress,and alterations in ion homeostasis,especially calcium transients[1].In Military Medical Research,Jiang et al.[2]sought to determine the functional role of complement factor D(Adipsin)in the pathophysiology of diabetic cardiomyopathy.
文摘目的探讨肝脏补体因子D(complement factor D,CFD)对高脂饮食小鼠肥胖及脂肪组织代谢紊乱的调控作用及具体机制。方法C57BL/6J小鼠经高脂饮食诱导肥胖,联合尾静脉或靶向定位注射病毒,构建组织特异性过表达或敲低模型,脂肪组织苏木精-伊红(hematoxylin-eosin,HE)染色观察脂肪组织细胞大小和数目,免疫组织化学染色评估解偶联蛋白1(uncoupling protein 1,UCP1)的蛋白表达,qPCR、Western印迹法检测脂肪组织脂质合成、产热相关基因及下游信号通路蛋白的表达;3T3-L1细胞系及原代棕色脂肪组织基质血管组分诱导分化后,经CFD重组蛋白联合下游通路抑制剂处理验证机制。结果肝脏特异性过表达CFD的小鼠在高脂喂养下脂肪组织体重占比增加,胰岛素抵抗加重,较对照组表现出更显著的脂肪堆积和能耗降低等代谢异常,而肝脏特异性敲低CFD可改善这些表型;机制层面,CFD通过激活脂肪细胞中C5aR-AKT信号通路发挥其代谢调控效应,靶向脂肪组织敲低C5aR可拮抗肝脏CFD过表达诱发的负面效应。结论肝脏CFD在肥胖及相关代谢紊乱中起关键作用,为肥胖相关代谢性疾病治疗策略提供新的干预靶点。
