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Beige adipocytes mediate the neuroprotective and anti-inflammatory effects of subcutaneous fat in obese mice
Nature Communications ( IF 16.6 ) Pub Date : 2021-07-30 , DOI: 10.1038/s41467-021-24540-8
De-Huang Guo 1 , Masaki Yamamoto 1 , Caterina M Hernandez 2 , Hesam Khodadadi 3 , Babak Baban 3, 4 , Alexis M Stranahan 1
Affiliation  

Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.



中文翻译:

米色脂肪细胞介导肥胖小鼠皮下脂肪的神经保护和抗炎作用

内脏肥胖会增加人类认知能力下降的风险,但皮下肥胖不会。在这里,我们报告米色脂肪细胞对于皮下脂肪的神经保护和抗炎作用是必不可少的。缺乏功能性米色脂肪的小鼠表现出加速的认知功能障碍和饮食肥胖的小胶质细胞激活。皮下脂肪移植还通过米色脂肪依赖性机制防止野生型小鼠的慢性肥胖。米色脂肪细胞在移植后恢复海马突触可塑性,这些作用需要抗炎细胞因子白细胞介素 4 (IL4)。在观察到脑膜 T 细胞中米色脂肪介导的 IL4 诱导后,我们研究了外周淋巴细胞在供体脂肪中的作用。脂肪和大脑之间没有供体来源的淋巴细胞运输的迹象,但移植对认知和小胶质细胞形态的影响需要受体来源的淋巴细胞。这些发现表明,米色脂肪细胞对抗肥胖引起的认知障碍,IL4 在米色脂肪和大脑功能之间的关系中具有潜在作用。

更新日期:2021-07-30
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