Wnt10b inhibits development of white and brown adipose tissues
Wnt10b inhibits development of white and brown adipose tissues
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DOI：
10.1074/jbc.m402937200
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发表时间：
2004-08-20
影响因子：
4.8
通讯作者：
MacDougald, OA
中科院分区：
文献类型：
--
作者：
Longo, KA;Wright, WS;MacDougald, OA
Wnt是调节多种发育过程的分泌信号蛋白家族。Wnt 10 b激活经典Wnt信号抑制体外前脂肪细胞分化为了确定Wnt信号传导是否在体内阻断脂肪形成，我们创建了转基因小鼠，其中Wnt 10 b从FABP 4启动子表达。Wnt 10 b在脂肪中的表达损害了这种组织在整个身体中的发育，总体脂肪减少了约50%，附睾和肾周贮库的重量减少了约60%。FABP 4-Wnt 10 b小鼠在喂食高脂肪饮食时抵抗脂肪组织的积累。此外，转基因小鼠比野生型小鼠更耐葡萄糖和胰岛素敏感。从FABP 4启动子表达Wnt 10 b也阻断棕色脂肪组织的发育。FABP 4-Wnt 10 b小鼠的肩胛间组织具有白色脂肪组织的视觉外观，但既不表达棕色（例如解偶联蛋白1）也不表达白色脂肪细胞标志物。转基因小鼠在寒冷的环境中无法保持核心体温，这进一步证明了Wnt 10 b抑制棕色脂肪组织的发育。虽然FABP 4-Wnt 10 b小鼠的食物摄入量没有改变，但耗氧量降低。因此，FABP 4-Wnt 10 b小鼠的食物饮食比对照组增加更多的体重，主要是因为皮肤重量的增加。总之，Wnt 10 b对白色和棕色脂肪组织发育的抑制导致无脂肪营养不良性糖尿病的瘦小鼠。
Wnt is a family of secreted signaling proteins that regulate diverse developmental processes. Activation of canonical Wnt signaling by Wnt10b inhibits differentiation of preadipocytes in vitro. To determine whether Wnt signaling blocks adipogenesis in vivo, we created transgenic mice in which Wnt10b is expressed from the FABP4 promoter. Expression of Wnt10b in adipose impairs development of this tissue throughout the body, with a decline of similar to50% in total body fat and a reduction of similar to60% in weight of epididymal and perirenal depots. FABP4-Wnt10b mice resist accumulation of adipose tissue when fed a high fat diet. Furthermore, transgenic mice are more glucose-tolerant and insulin-sensitive than wild type mice. Expression of Wnt10b from the FABP4 promoter also blocks development of brown adipose tissue. Interscapular tissue of FABP4-Wnt10b mice has the visual appearance of white adipose tissue but expresses neither brown (e.g. uncoupling protein 1) nor white adipocyte markers. Transgenic mice are unable to maintain a core body temperature when placed in a cold environment, providing further evidence that Wnt10b inhibits development of brown adipose tissue. Although food intake is not altered in FABP4-Wnt10b mice, oxygen consumption is decreased. Thus, FABP4-Wnt10b mice on a chow diet gain more weight than controls, largely because of an increase in weight of skin. In summary, inhibition by Wnt10b of white and brown adipose tissue development results in lean mice without lipodystrophic diabetes.