The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity by Regulating Gut Microbiota Homeostasis.
The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity by Regulating Gut Microbiota Homeostasis.
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DOI：
10.1016/j.chom.2018.08.009
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发表时间：
2018-09-12
影响因子：
30.3
通讯作者：
Ting JP
中科院分区：
文献类型：
--
作者：
Truax AD;Chen L;Tam JW;Cheng N;Guo H;Koblansky AA;Chou WC;Wilson JE;Brickey WJ;Petrucelli A;Liu R;Cooper DE;Koenigsknecht MJ;Young VB;Netea MG;Stienstra R;Sartor RB;Montgomery SA;Coleman RA;Ting JP
除了高脂肪饮食（HFD）和不活动之外，炎症和微生物群组成也会导致肥胖。抑制性免疫受体，如NLRP 12，抑制炎症，对解决炎症很重要，但它们在肥胖中的作用尚不清楚。我们发现人类肥胖与脂肪组织NLRP 12表达减少相关。类似地，Nlrp 12-/-小鼠显示增加的体重增加、脂肪沉积、血糖、NF-κB/MAPK活化和M1-巨噬细胞极化。此外，需要NLRP 12来减轻HFD诱导的炎性小体活化。与野生型动物共饲养，抗生素治疗或无菌条件足以抑制Nlrp 12-/-小鼠的炎症，肥胖和胰岛素耐受性，涉及微生物群。HFD喂养的Nlrp 12-/-小鼠表现出以肥胖相关丹毒菌科增加为标志的生态失调，但毛螺菌科和短链脂肪酸（SCFA）合成所需的相关酶减少。施用毛螺菌科或SCFA减轻肥胖、炎症和生态失调。这些发现表明，Nlrp 12通过维持有益的微生物群来减少HFD诱导的肥胖。Truax等人表明，骨髓表达的NLRP 12通过减弱脂肪组织中的TNF、IL-6、NF-kB、MAPK、M1巨噬细胞极化和炎性小体活化来抑制高脂饮食诱导的肥胖和2型糖尿病。NLRP 12的这种保护功能是微生物群依赖性的，并且与毛螺菌科及其代谢物相关，其减轻肥胖。
In addition to high-fat diet (HFD) and inactivity, inflammation and microbiota composition contribute to obesity. Inhibitory immune receptors, such as NLRP12, dampen inflammation and are important for resolving inflammation, but their role in obesity is unknown. We show that obesity in humans correlates with reduced expression of adipose tissue NLRP12. Similarly, Nlrp12-/- mice show increased weightgain, adipose deposition, blood glucose, NF-κB/MAPK activation and M1-macrophage polarization. Additionally, NLRP12 is required to mitigate HFD-induced inflammasome activation. Co-housing with wild-type animals, antibiotic treatment or germ-free condition was sufficient to restrain inflammation, obesity and insulin-tolerance in Nlrp12-/- mice, implicating the microbiota. HFD-fed Nlrp12-/- mice display dysbiosis marked by increased obesity-associated Erysipelotrichaceae, but reduced Lachnospiraceae family and the associated enzymes required for short-chain fatty acid (SCFA) synthesis. Lachnospiraceae or SCFA administration attenuates obesity, inflammation and dysbiosis. These findings reveal that Nlrp12 reduces HFD-induced obesity by maintaining beneficial microbiota. Truax et al. show that myeloid-expressed NLRP12 restrains high-fat diet-induced obesity and type 2 diabetes by attenuating TNF, IL-6, NF-kB, MAPK, M1 macrophage polarization and inflammasome activation in adipose tissue. This protective function of NLRP12 is microbiota dependent, and is associated with Lachnospiraceae and their metabolites, which mitigate obesity.
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影响因子：
16.6
作者：
Ballak, Dov B.;van Diepen, Janna A.;Stienstra, Rinke
通讯作者：
Stienstra, Rinke
影响因子：
--
作者：
Cho, Kae Won;Morris, David L.;Lumeng, Carey N.
通讯作者：
Lumeng, Carey N.
影响因子：
29.4
作者：
Bouter, Kristien E.;van Raalte, Daniel H.;Nieuwdorp, Max
通讯作者：
Nieuwdorp, Max
DOI：
10.1073/pnas.0504978102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Ley, RE;Bäckhed, F;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
30.3
作者：
Gevers D;Kugathasan S;Denson LA;Vázquez-Baeza Y;Van Treuren W;Ren B;Schwager E;Knights D;Song SJ;Yassour M;Morgan XC;Kostic AD;Luo C;González A;McDonald D;Haberman Y;Walters T;Baker S;Rosh J;Stephens M;Heyman M;Markowitz J;Baldassano R;Griffiths A;Sylvester F;Mack D;Kim S;Crandall W;Hyams J;Huttenhower C;Knight R;Xavier RJ
通讯作者：
Xavier RJ