Skeletal muscle provides a pro‐browning microenvironment for transplanted brown adipose tissue to maintain its effect to ameliorate obesity in ob/ob mice
Skeletal muscle provides a pro‐browning microenvironment for transplanted brown adipose tissue to maintain its effect to ameliorate obesity in ob/ob mice
复制标题
DOI：
10.1096/fj.202101144r
复制
发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Junrong Cai;Shenglu Jiang;Yuping Quan;Jia Lin;Shaowei Zhu;Jing Wang;Wenqing Jiang;Yunjun Liao;F. Lu
中科院分区：
文献类型：
--
作者：
Junrong Cai;Shenglu Jiang;Yuping Quan;Jia Lin;Shaowei Zhu;Jing Wang;Wenqing Jiang;Yunjun Liao;F. Lu
棕色脂肪组织(BAT)移植是一种有前景的提高全身能量代谢以改善肥胖的方法。然而，移植后BAT的变化以及受体部位微环境对移植物功能的影响尚未完全确定。因此，我们的目的是确定将C57BL/6小鼠的BAT移植到瘦素缺陷ob/ob小鼠的背侧皮下或股四头肌深处的效果。皮下移植的BAT在移植后16周失去了BAT的特征，表现出更多的炎性细胞浸润和更多的油囊。相比之下，肌肉下移植的蝙蝠保持了蝙蝠的特征，并且血运更丰富。有趣的是，肌肉下蝙蝠移植导致氧气消耗显著增加，皮下脂肪炎症减少，这与胰岛素抵抗和体重增加的长期减少有关，而皮下移植在16周后失败。这些结果表明，蝙蝠移植的有益效果取决于受体部位的微环境。骨骼肌可以提供一种微环境，在很长一段时间内保持蝙蝠移植物的固有特征，这有助于减少肥胖和改善血糖稳态。
Brown adipose tissue (BAT) transplantation is a promising means of increasing whole‐body energy metabolism to ameliorate obesity. However, the changes in BAT following transplantation and the effects of the microenvironment of the recipient site on graft function have yet to be fully characterized. Therefore, we aimed to determine the effects of transplanting BAT from C57BL/6 mice into the dorsal subcutaneous region or deep to the quadriceps femoris muscle of leptin‐deficient ob/ob mice. Subcutaneously transplanted BAT lost features of BAT and demonstrated greater inflammatory cell infiltration and more oil cysts 16 weeks following transplantation. By contrast, the sub‐muscularly transplanted BAT maintained features of BAT and was more highly vascularized. Interestingly, sub‐muscular BAT transplantation led to a significant increase in oxygen consumption and less inflammation in subcutaneous fat, which was associated with long‐term reductions in insulin resistance and body mass gain, whereas the subcutaneous transplants failed after 16 weeks. These results demonstrate that the beneficial effects of BAT transplantation depend upon the microenvironment of the recipient site. Skeletal muscle may provide a microenvironment that maintains the inherent features of BAT grafts over a long period of time, which facilitates a reduction in obesity and improvements in glucose homeostasis.