Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice.
Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice.
复制标题
DOI：
10.1038/nm.4031
复制
发表时间：
2016-03
期刊：
影响因子：
82.9
通讯作者：
Corvera S
中科院分区：
文献类型：
--
作者：
Min SY;Kady J;Nam M;Rojas-Rodriguez R;Berkenwald A;Kim JH;Noh HL;Kim JK;Cooper MP;Fitzgibbons T;Brehm MA;Corvera S
解偶联蛋白1(UCP1)在棕色脂肪组织中高度表达，它通过解偶联ATP产生的电子传递来产生热量。UCP1也在经典的棕色脂肪组织库外被发现，存在于被称为“白褐色”或“米色”的脂肪细胞中。在人类中，“棕色/棕色”脂肪细胞的存在与瘦削、代谢健康的表型相关，但是否存在因果关系尚不清楚。在这里，我们报告了人类‘棕色/棕色’脂肪细胞前体细胞对促血管生成因子的反应，伴随着毛细血管网络的扩大而增殖。由这些前体细胞形成的脂肪细胞对腺苷酸环化酶激活做出反应，从UCP1阴性转变为UCP1阳性，腺苷环化酶是‘米色/褐褐色’表型的一个明显特征，并显示出不耦合的呼吸。当移植到正常或高脂饮食喂养的糖耐量不高的NOD-SCID IL2rgnull小鼠体内时，激活的‘Brite/Beige’脂肪细胞提高了系统的葡萄糖耐量。这些脂肪细胞表达神经内分泌和分泌因子，包括与人类肥胖密切相关的原蛋白转换酶PCSK1。因此，促血管生成条件推动人类‘米色/棕褐色’脂肪细胞前体细胞的增殖，而激活的‘米色/棕褐色’脂肪细胞可能通过神经内分泌机制影响全身葡萄糖稳态。
The uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes termed ‘brite’ (brown-in-white) or ‘beige’. In humans, the presence of ‘brite/beige’ adipocytes correlates with a lean, metabolically healthy phenotype, but whether a causal relationship exists is not clear. Here we report that human ‘brite/beige’ adipocyte progenitors proliferate in response to pro-angiogenic factors, in association with expanding capillary networks. Adipocytes formed from these progenitors transform from being UCP1-negative to UCP1-positive in response to adenylate cyclase activation, a defining feature of the ‘beige/brite’ phenotype, and display uncoupled respiration. When implanted into normal or high fat diet-fed, glucose intolerant NOD-scid IL2rgnull mice, activated ‘brite/beige’ adipocytes enhance systemic glucose tolerance. These adipocytes express neuroendocrine and secreted factors, including the pro-protein convertase PCSK1, which is strongly associated with human obesity. Thus, pro-angiogenic conditions drive proliferation of human ‘beige/brite’ adipocyte progenitors, and activated ‘beige/brite’ adipocytes can affect systemic glucose homeostasis, potentially through a neuroendocrine mechanism.