Myeloid Krüppel-like factor 2 is a critical regulator of metabolic inflammation.
Myeloid Krüppel-like factor 2 is a critical regulator of metabolic inflammation.
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DOI：
10.1038/s41467-020-19760-3
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发表时间：
2020-11-18
影响因子：
16.6
通讯作者：
Jain MK
中科院分区：
文献类型：
--
作者：
Sweet DR;Vasudevan NT;Fan L;Booth CE;Keerthy KS;Liao X;Vinayachandran V;Takami Y;Tugal D;Sharma N;Chan ER;Zhang L;Qing Y;Gerson SL;Fu C;Wynshaw-Boris A;Sangwung P;Nayak L;Holvoet P;Matoba K;Lu Y;Zhou G;Jain MK
大量证据表明代谢组织和免疫系统之间的相互作用在肥胖的发生和进展中。然而，协调中枢和外周代谢炎症的分子调节因子仍不完全清楚。在这里，我们确定髓样 Krüppel 样因子 2 (KLF2) 是肥胖及其后遗症的重要调节因子。在小鼠和人类中，摄入脂肪饮食会下调骨髓 KLF2 水平。在基础条件下，骨髓特异性 KLF2 敲除小鼠 (K2KO) 表现出摄食和体重增加的增加。高脂肪饮食 (HFD) 喂养进一步加剧 K2KO 代谢疾病表型。从机制上讲，髓系 KLF2 的缺失会增加外周和中枢组织的代谢炎症。配对喂养、骨髓移植和小胶质细胞消融的结合表明中枢和外周对观察到的 K2KO 诱导的代谢功能障碍有贡献。最后，骨髓 KLF2 的过度表达可以保护小鼠免受 HFD 诱导的肥胖和胰岛素抵抗。总之，这些数据表明骨髓 KLF2 作为稳态和疾病中中枢和外周代谢炎症的节点调节因子。炎症通过不完全了解的机制促进代谢疾病的发展。作者在此报告称，删除骨髓细胞中的转录因子 KLF2 会导致伴有外周和中枢组织炎症的小鼠进食量增加和体重增加，而过度表达则可以预防饮食诱导的代谢疾病。
Substantial evidence implicates crosstalk between metabolic tissues and the immune system in the inception and progression of obesity. However, molecular regulators that orchestrate metaflammation both centrally and peripherally remains incompletely understood. Here, we identify myeloid Krüppel-like factor 2 (KLF2) as an essential regulator of obesity and its sequelae. In mice and humans, consumption of a fatty diet downregulates myeloid KLF2 levels. Under basal conditions, myeloid-specific KLF2 knockout mice (K2KO) exhibit increased feeding and weight gain. High-fat diet (HFD) feeding further exacerbates the K2KO metabolic disease phenotype. Mechanistically, loss of myeloid KLF2 increases metaflammation in peripheral and central tissues. A combination of pair-feeding, bone marrow-transplant, and microglial ablation implicate central and peripheral contributions to K2KO-induced metabolic dysfunction observed. Finally, overexpression of myeloid KLF2 protects mice from HFD-induced obesity and insulin resistance. Together, these data establish myeloid KLF2 as a nodal regulator of central and peripheral metabolic inflammation in homeostasis and disease. Inflammation contributes to the development of metabolic disease through incompletely understood mechanisms. Here the authors report that deletion of the transcription factor KLF2 in myeloid cells leads to increased feeding and weight gain in mice with concomitant peripheral and central tissue inflammation, while overexpression protects against diet-induced metabolic disease.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
29
作者：
Ellacott KL;Morton GJ;Woods SC;Tso P;Schwartz MW
通讯作者：
Schwartz MW
影响因子：
13.5
作者：
Kim, Seung-Jin;Feng, Dechun;Gao, Bin
通讯作者：
Gao, Bin
影响因子：
64.5
作者：
Perry RJ;Camporez JG;Kursawe R;Titchenell PM;Zhang D;Perry CJ;Jurczak MJ;Abudukadier A;Han MS;Zhang XM;Ruan HB;Yang X;Caprio S;Kaech SM;Sul HS;Birnbaum MJ;Davis RJ;Cline GW;Petersen KF;Shulman GI
通讯作者：
Shulman GI