钙黏素Clstn3介导的交感神经-脂肪细胞连接调控能量代谢的机制研究
结题报告
批准号:
81974122
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
杨颖
依托单位:
学科分类:
脂肪组织生理调控与功能异常
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
杨颖
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中文摘要
棕色脂肪活化和白色脂肪棕色化有利于改善机体能量代谢,此过程伴随交感神经分布和活动的增加。最近报道神经末梢可直接与脂肪细胞形成突触样连接,但调控其形成的分子机制尚不明确。Clstn3是钙黏素家族成员,分布于突触后膜,通过聚集突触前蛋白促进突触发育和诱导突触前膜释放神经递质。目前有关Clstn3的研究都集中在中枢神经元,其在脂肪中的研究未见报道。我们前期发现Clstn3在棕色脂肪高表达,主要定位于脂肪细胞的胞膜和周围;冷暴露后小鼠棕色及皮下脂肪中Clstn3表达上调,而在肥胖个体皮下脂肪中表达减少;通过构建脂肪特异性Clstn3敲除小鼠,初步发现小鼠棕/米色脂肪中的交感神经分布减少、体温下降、产热功能受损。我们推测脂肪组织Clstn3可能通过胞外段结构作用于交感神经,介导脂肪细胞和交感神经的连接串话。本项目将深入研究Clstn3通过何种方式调节交感神经活动,进而影响脂肪功能和能量代谢。
英文摘要
Adipose tissues can be divided into three distinct types: white adipose tissue (WAT), brown adipose tissue (BAT) and beige fat. Growing evidence suggests that BAT activation and the development of beige fat, also called browning of WAT, protect against obesity and improve energy metabolism. This process is accompanied by an obvious increase in distribution and activity of sympathetic arborizations. These sympathetic fibers can directly form synaptic-like structures with adipocytes, but the key molecular and mechanism mediating the formation of sympathetic neuro-adipose connections are currently unclear. Clstn3 is a member of cadherin superfamily belonging to cell adhesion molecules (CAMs), which was highly expressed in brain. It has been reported that Clstn3 can promote synapse development and induce presynaptic terminals releasing neurotransmitter by clustering a number of different presynaptic proteins in contacting axons. The expression and function of Clstn3 in sympathetically enriched adipose tissue has not been researched. Our previous work found that Clstn3 was highly expressed in adipocytes from BAT and beige fat, and localized to its membrane and surrounding, indicating that it may mediate the crosstalk between adipocytes and extracellular components; The expression levels of Clstn3 was up-regulated in WAT and BAT but not in brain when mice were exposed to cold and down-regulated in subcutaneous fat of obese men and high fat diet fed mice. The core body temperature of adipose tissue-specific Clstn3 knockout mice was lower than control mice under cold exposure. In addition, the Clstn3 knockout model also exhibited reduced distribution of sympathetic nerves and impaired thermogenic function of BAT and WAT, suggesting that Clstn3 might participate in the regulation of energy metabolism by influencing sympathetic activity. However, the molecular mechanism is still unclear. Therefore, we will delve into/study how the adipocyte-derived Clstn3 regulates the distribution and activity of sympathetic nerves, which in turn affects adipose tissue function and metabolism.
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DOI:10.1080/21623945.2022.2091206
发表时间:2022-12
期刊:Adipocyte
影响因子:3.3
作者:
通讯作者:
DOI:10.1016/j.molmet.2022.101446
发表时间:2022-04
期刊:Molecular metabolism
影响因子:8.1
作者:Alimujiang M;Sun J;Chen S;Bai N;Chen S;Hu F;Ma J;Xu Y;Xu J;Ma X;Yang Y
通讯作者:Yang Y
DOI:10.1016/j.molmet.2022.101531
发表时间:2022-09
期刊:MOLECULAR METABOLISM
影响因子:8.1
作者:Bai, Ningning;Lu, Xuhong;Jin, Li;Alimujiang, Miriayi;Ma, Jingyuan;Hu, Fan;Xu, Yuejie;Sun, Jingjing;Xu, Jun;Zhang, Rong;Han, Junfeng;Hu, Cheng;Yang, Ying
通讯作者:Yang, Ying
DOI:10.1093/lifemeta/load037
发表时间:2023
期刊:Life Metabolism
影响因子:--
作者:Ningning Bai;Xuhong Lu;Yansu Wang;Xiaoya Li;Rong Zhang;Haoyong Yu;Cheng Hu;Xiaojing Ma;Yuqian Bao;Ying Yang
通讯作者:Ying Yang
DOI:doi: 10.3389/fendo.2020.592154
发表时间:2021
期刊:frontiers in Endocrinology
影响因子:--
作者:Ningning Bai;Jingyuan Ma;Miriayi Alimujiang;Jun Xu;Fan Hu;Yuejie Xu;Qingyang Leng;Shuqing Chen;Xiaohua Li;Junfeng Han;Weiping Jia;Yuqian Bao;Ying Yang
通讯作者:Ying Yang
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海外基金