Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity.
Apelin inhibits diet-induced obesity by enhancing lymphatic and blood vessel integrity.
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Apelin通过增强淋巴和血管完整性来抑制饮食诱导的肥胖症。
DOI：
10.2337/db12-0604
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发表时间：
2013-06
期刊：
影响因子：
7.7
通讯作者：
Takakura N
中科院分区：
文献类型：
--
作者：
Sawane M;Kajiya K;Kidoya H;Takagi M;Muramatsu F;Takakura N
血管生成与脂肪组织的生长密切相关，导致肥胖，肥胖是2型糖尿病和高血压的风险因素，主要是因为扩张的脂肪组织需要增加来自血管的营养供应。因此，脂肪因子诱导血管异常已经得到了很好的研究，而血管功能改变如何促进肥胖还相对未被探索。此外，存活下来的Prox1杂合子小鼠表现出异常的淋巴模式和成年后出现的肥胖，这表明脂肪细胞的积累可能与淋巴功能密切相关。在这里，我们提出了一种新的减肥策略，该策略基于使用apelin增强淋巴管和血管的完整性。喂食高脂饮食(HFD)的apelin基因敲除(KO)小鼠表现出肥胖表型，并伴有淋巴管和血管的异常增大。HFD中的脂肪酸诱导内皮细胞高通透性，导致脂肪细胞分化，而apelin促进血管稳定。此外，用选择性环氧合酶-2抑制剂塞来昔布治疗apelin KO小鼠，再给它们喂食HFD，可以改善血管功能，还可以减轻肥胖。最后，apelin转基因小鼠表现出皮下脂肪组织的减少，这归因于抑制了HFD诱导的血管高通透性。这些结果表明，Apelin通过增强血管完整性来抑制HFD诱导的肥胖。Apelin可以作为治疗肥胖症和相关疾病的靶点。
Angiogenesis is tightly associated with the outgrowth of adipose tissue, leading to obesity, which is a risk factor for type 2 diabetes and hypertension, mainly because expanding adipose tissue requires an increased nutrient supply from blood vessels. Therefore, induction of vessel abnormality by adipokines has been well-studied, whereas how altered vascular function promotes obesity is relatively unexplored. Also, surviving Prox1 heterozygous mice have shown abnormal lymphatic patterning and adult-onset obesity, indicating that accumulation of adipocytes could be closely linked with lymphatic function. Here, we propose a new antiobesity strategy based on enhancement of lymphatic and blood vessel integrity with apelin. Apelin knockout (KO) mice fed a high-fat diet (HFD) showed an obese phenotype associated with abnormal lymphatic and blood vessel enlargement. Fatty acids present in the HFD induced hyperpermeability of endothelial cells, causing adipocyte differentiation, whereas apelin promoted vascular stabilization. Moreover, treatment of apelin KO mice with a selective cyclooxygenase-2 inhibitor, celecoxib, that were fed an HFD improved vascular function and also attenuated obesity. Finally, apelin transgenic mice showed decreased subcutaneous adipose tissue attributable to inhibition of HFD-induced hyperpermeability of vessels. These results indicate that apelin inhibits HFD-induced obesity by enhancing vessel integrity. Apelin could serve as a therapeutic target for treating obesity and related diseases.
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影响因子：
120.1
作者：
Cao, Yihai
通讯作者：
Cao, Yihai
影响因子：
6
作者：
Hirakawa, S;Hong, YK;Detmar, M
通讯作者：
Detmar, M
DOI：
10.1006/bbrc.1998.9489
发表时间：
1998-10-20
影响因子：
3.1
作者：
Tatemoto, K;Hosoya, M;Fujino, M
通讯作者：
Fujino, M
影响因子：
6.5
作者：
Kajiya, Kentaro;Sawane, Mika;Detmar, Michael
通讯作者：
Detmar, Michael
DOI：
10.1084/jem.20100559
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huggenberger R;Ullmann S;Proulx ST;Pytowski B;Alitalo K;Detmar M
通讯作者：
Detmar M