中文摘要
激活白色脂肪棕色化在防治肥胖及相关代谢性疾病中起重要作用。脂肪组织血管新生与白色脂肪棕色化密切相关,肌肉组织分泌的多肽类激素Irisin通过血液循环到达脂肪组织诱导白色脂肪棕色化,但是,Irisin、脂肪组织血管新生及白色脂肪棕色化三者间的关系及其作用机制的研究目前尚未有文献报道,迫切需要新颖的分子影像和结构功能成像对上述过程进行活体无创准确评估。本项目拟构建双功能、双模态分子探针靶向脂肪组织新生血管内皮αvβ3整合素受体并利用脂肪组织内弱酸环境下pH控释Irisin,采用超高场7.0T磁共振仪及近红外光学成像仪,从分子水平、脂肪组织脂质含量水平及微循环灌注水平建立一站式活体磁共振/近红外评价体系,探讨Irisin在高脂饮食诱导下脂肪组织血管新生及白色脂肪棕色化过程中的作用及相关机制,为Irisin进一步临床试验提供理论依据。
英文摘要
Activation of browning of white adipose tissue may play an important role in prevention and therapy of obisity and metabolic syndrome. There is a strong relationship among irisin, the adipose tissue angiogenesis and browning of white adipose tissue. Irisin is secreted as a newly identified hormone from the muscle to circulation and acts on white adipose cell to promote browning of white adipose tissue. However, it is still unclear about the irisin-mediated exact mechanisms in adipose tissue angiogenesis and browning of white adipose tissue. It is urgently needed to search imaging biomarker and MR imaging methods to enable non-invasive accurate detection of the procession of browning of white adipose tissue. However, such imaging techniques are not still established. Thus, to dynamically demonstrate the relations and potential mechanisms among the Irisin, angiogenesis and browning of white adipose tissue, we plan to design and synthesize the novel probe that has RGD cyclic peptide to targeted αvβ3 on angiogenesis and Irisin to be transported and delivered in adipose tissue based on the local pH value. This project is also to develop a one-stop MR evaluation system to noninvasively monitor the lipid content in white and brown adipose tissue, the adipose tissue angiogenesis and browning of white adipose tissue in the structural, functional and molecular level in a mouse model after high fat diet at 7.0T micro-MR scanner and near infrared scanner. All the changes and relations will be evaluated in vivo, which will provide evidences for future clinical studies.
