Diet induced obesity is independent of metabolic endotoxemia and TLR4 signalling, but markedly increases hypothalamic expression of the acute phase protein, SerpinA3N.
Diet induced obesity is independent of metabolic endotoxemia and TLR4 signalling, but markedly increases hypothalamic expression of the acute phase protein, SerpinA3N.
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DOI：
10.1038/s41598-018-33928-4
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发表时间：
2018-10-23
影响因子：
4.6
通讯作者：
Morgan PJ
中科院分区：
文献类型：
--
作者：
Dalby MJ;Aviello G;Ross AW;Walker AW;Barrett P;Morgan PJ
下丘脑炎症被认为是导致肥胖的原因。一种潜在的机制是通过肠道微生物群来源的细菌脂多糖（LPS）进入循环并激活Toll样受体-4。这被称为代谢性内毒素血症。另一个潜在的机制是持续暴露于高脂饮食（HFD）超过12周引起的全身性炎症。在这项研究中，我们表明，小鼠喂养HFD超过8周变得肥胖，并显示血浆LPS结合蛋白升高，但体重增加和肥胖症并没有在缺乏Tlr 4或其共同受体Cd 14的小鼠中减弱。此外，盲肠微生物群组成在饮食中保持不变。将小鼠暴露于HFD更长时间（20周）以驱动全身炎症也会导致肥胖。用于评估这些小鼠下丘脑炎症的RNAseq显示，响应于HFD，Serpina 3 n和Socs 3的下丘脑表达增加，几乎没有其他基因改变。原位杂交证实了ARC和DMH在20周时以及在8周时Serpina 3 n和Socs 3表达增加，并且早在HFD 1周时就可以检测到SerpinA 3 N蛋白增加。总的来说，这些数据表明HFD没有引起下丘脑炎症，代谢性内毒素血症与肥胖无关。
Hypothalamic inflammation is thought to contribute to obesity. One potential mechanism is via gut microbiota derived bacterial lipopolysaccharide (LPS) entering into the circulation and activation of Toll-like receptor-4. This is called metabolic endotoxemia. Another potential mechanism is systemic inflammation arising from sustained exposure to high-fat diet (HFD) over more than 12 weeks. In this study we show that mice fed HFD over 8 weeks become obese and show elevated plasma LPS binding protein, yet body weight gain and adiposity is not attenuated in mice lacking Tlr4 or its co-receptor Cd14. In addition, caecal microbiota composition remained unchanged by diet. Exposure of mice to HFD over a more prolonged period (20 weeks) to drive systemic inflammation also caused obesity. RNAseq used to assess hypothalamic inflammation in these mice showed increased hypothalamic expression of Serpina3n and Socs3 in response to HFD, with few other genes altered. In situ hybridisation confirmed increased Serpina3n and Socs3 expression in the ARC and DMH at 20-weeks, but also at 8-weeks and increased SerpinA3N protein could be detected as early as 1 week on HFD. Overall these data show lack of hypothalamic inflammation in response to HFD and that metabolic endotoxemia does not link HFD to obesity.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
DOI：
10.1046/j.1365-2362.2001.00792.x
发表时间：
2001-02-01
影响因子：
5.5
作者：
Drewe, J;Beglinger, C;Fricker, G
通讯作者：
Fricker, G
影响因子：
5.6
作者：
Davis, Jeremy E.;Braucher, Douglas R.;Spurlock, Michael E.
通讯作者：
Spurlock, Michael E.
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：
24.5
作者：
Cani PD;Possemiers S;Van de Wiele T;Guiot Y;Everard A;Rottier O;Geurts L;Naslain D;Neyrinck A;Lambert DM;Muccioli GG;Delzenne NM
通讯作者：
Delzenne NM