Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice.
Intestinal epithelial cell-specific Raptor is essential for high fat diet-induced weight gain in mice.
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DOI：
10.1016/j.bbrc.2018.10.040
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发表时间：
2018-11-10
影响因子：
3.1
通讯作者：
Guo J
中科院分区：
文献类型：
--
作者：
Onufer EJ;Tay S;Barron LK;Courtney CM;Warner BW;Guo J
哺乳动物雷帕霉素复合体靶标1(MTORC1)是细胞生长和增殖的主要调节因子，通过燃料感应调节细胞生长和增殖。对mTOR的系统性抑制及其下游产物的操纵可以防止饮食诱导的肥胖。这项研究的目的是确定肠靶向mTORC1抑制的后果。为了减弱肠道mTORC 1的活性，将维林-克里尔小鼠与Raptorflx/FLOX小鼠杂交，创建了肠道特异的猛禽零点系(I-Raptor−/−)。小鼠被喂以高脂肪饮食(HFD)，并评估其成分变化和食物摄入量水平。在五周的时间过程中，与野生型(WT)小鼠相比，I-Raptor−/−小鼠在服用高脂饮食后体重持续增加，这是因为显著减少了食物摄入量。重要的是，i-Raptor−/−小鼠并没有表现出营养不良的迹象，这一点从它们保持瘦小的身体质量上得到了证明。I-Raptor−/−小鼠也保持了正常的代谢特征，甘油三酯或空腹血糖水平没有明显变化。进一步的研究表明，饥饿一夜后补充高脂饲料可显著增强I-Raptor−/−肠上皮细胞GDF-15mRNA的表达。综上所述，我们的研究证实，肠道特异性mTORC1的丢失通过减少食物摄入量而不改变代谢谱来保护饮食诱导的肥胖的发展。
Mammalian target of rapamycin complex 1 (mTORC1) is a major regulator of cell growth and proliferation through fuel sensing. Systemic inhibition of mTOR as well as manipulation of its downstream products prevent diet-induced obesity. The purpose of this study was to determine the consequences of intestine-targeted mTORC1 inhibition. To attenuate intestinal mTORC1 activity, Villin-CreER mice were crossed with Raptorflox/flox mice, creating an intestinal-specific Raptor null line (i-Raptor −/−). Mice were fed a high fat diet (HFD) and compositional changes as well as food intake levels were assessed. Over a five-week time course, i-Raptor −/− mice consistently gained less body weight on a HFD compared to wildtype (WT) mice secondary to significantly reduced food intake. Importantly, the i-Raptor −/− mice did not appear to be malnourished, demonstrated by their preservation of lean body mass. i-Raptor −/− mice also maintained a normal metabolic profile without significant changes in triglyceride or fasting glucose levels. Further investigation revealed that GDF-15 mRNA expression was significantly enhanced in i-Raptor −/− enterocytes when refed with HFD after overnight starvation. In summary, our study establishes that loss of intestinal specific-mTORC1 is protective of the development of diet-induced obesity by reducing food intake without altering the metabolic profile.
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影响因子：
82.9
作者：
Emmerson, Paul J.;Wang, Feng;Wu, Xinle
通讯作者：
Wu, Xinle
影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
影响因子：
4.8
作者：
Kaizuka, Takeshi;Hara, Taichi;Mizushima, Noboru
通讯作者：
Mizushima, Noboru
影响因子：
16
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
通讯作者：
Sabatini, DM
DOI：
10.1083/jcb.200408161
发表时间：
2004-11-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Manning BD
通讯作者：
Manning BD