Zhao Junxing, Yang Qiyuan, Zhang Lupei, Liang Xingwei, Sun Xiaofei, Wang Bo, Chen Yanting, Zhu Meijun, Du Min
Department of Animal Sciences and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030800, China; Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
Biochem Biophys Res Commun. 2017 Sep 16;491(2):508-514. doi: 10.1016/j.bbrc.2017.06.149. Epub 2017 Jun 28.
Brown adipose tissue (BAT) dissipates energy for thermogenesis which reduces or prevents obesity and metabolic dysfunction. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism and its activity is inhibited in the developing BAT due to obesity. We previously found that AMPK is required for brown fat development and thermogenic function, but the non-brown adipogenic differentiation of progenitor cells due to AMPKα1 deficiency has not been defined. We found that, in vivo, the thermogenic capacity and morphology of BAT were compromised due to AMPK deficiency, which was correlated with decreased progenitor density in BAT. In addition, the expression of fibrogenic markers was higher in AMPK deficient compared to wild-type mice. Furthermore, we transplanted AMPKα1 wild-type (WT) and floxed BAT into the same recipient mice; following tamoxifen induced AMPKα1 knockout in floxed BAT, the fibrogenesis was enhanced compared to WT mice. Taken together, our data demonstrated that AMPKα1 deficiency suppressed brown adipogenesis in favor of fibrogenesis during BAT development.
棕色脂肪组织（BAT）通过产热消耗能量，从而减轻或预防肥胖和代谢功能障碍。AMP激活的蛋白激酶（AMPK）是能量代谢的主要调节因子，在发育中的BAT中，其活性因肥胖而受到抑制。我们之前发现，AMPK是棕色脂肪发育和产热功能所必需的，但尚未明确由于AMPKα1缺乏导致的祖细胞非棕色脂肪生成分化情况。我们发现，在体内，由于AMPK缺乏，BAT的产热能力和形态受到损害，这与BAT中祖细胞密度降低相关。此外，与野生型小鼠相比，AMPK缺乏小鼠中纤维化标志物的表达更高。此外，我们将AMPKα1野生型（WT）和floxed BAT移植到同一受体小鼠中；在他莫昔芬诱导floxed BAT中的AMPKα1基因敲除后，与WT小鼠相比，纤维化增强。综上所述，我们的数据表明，在BAT发育过程中，AMPKα1缺乏抑制棕色脂肪生成，有利于纤维化形成。
