A brain-to-gut signal controls intestinal fat absorption
文献类型：期刊论文
| 作者 | Lyu, Qianqian7,8; Xue, Wenzhi6,8; Liu, Ruixin7,8; Ma, Qinyun7,8; Kasaragod, Vikram Babu1; Sun, Shan5; Li, Qian8; Chen, Yanru8; Yuan, Mingyang8; Yang, Yuying8 |
| 刊名 | NATURE
 |
| 出版日期 | 2024-09-11 |
| 页码 | 27 |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/s41586-024-07929-5 |
| 通讯作者 | Wang, Jiqiu(wangjq@shsmu.edu.cn) ; Wang, Weiqing(wqingw@shsmu.edu.cn) |
| 英文摘要 | Although fat is a crucial source of energy in diets, excessive intake leads to obesity. Fat absorption in the gut is prevailingly thought to occur organ-autonomously by diffusion1-3. Whether the process is controlled by the brain-to-gut axis, however, remains largely unknown. Here we demonstrate that the dorsal motor nucleus of vagus (DMV) plays a key part in this process. Inactivation of DMV neurons reduces intestinal fat absorption and consequently causes weight loss, whereas activation of the DMV increases fat absorption and weight gain. Notably, the inactivation of a subpopulation of DMV neurons that project to the jejunum shortens the length of microvilli, thereby reducing fat absorption. Moreover, we identify a natural compound, puerarin, that mimics the suppression of the DMV-vagus pathway, which in turn leads to reduced fat absorption. Photoaffinity chemical methods and cryogenic electron microscopy of the structure of a GABAA receptor-puerarin complex reveal that puerarin binds to an allosteric modulatory site. Notably, conditional Gabra1 knockout in the DMV largely abolishes puerarin-induced intestinal fat loss. In summary, we discover that suppression of the DMV-vagus-jejunum axis controls intestinal fat absorption by shortening the length of microvilli and illustrate the therapeutic potential of puerarin binding to GABRA1 in fat loss. Neurons in the dorsal motor nucleus of vagus are involved in the absorption of fat in the intestine, and the natural compound puerarin shows utility in modulating this brain-gut axis to reduce fat absorption. |
| WOS关键词 | RECEPTORS ; NEURONS ; HETEROGENEITY ; MODULATION ; MOTILITY ; NUCLEUS ; PROTEIN ; TOOLS |
| 资助项目 | National Natural Science Foundation of China[92157204] ; National Natural Science Foundation of China[82250901] ; National Natural Science Foundation of China[81930021] ; National Natural Science Foundation of China[91857205] ; National Natural Science Foundation of China[82100905] ; National Key Research and Development Program of China[2022YFC2505201] ; National Key Research and Development Program of China[2021YFA1301103] ; Shanghai Municipal Education Commission[2023ZKZD22] ; Science and Technology Commission of Shanghai Municipality[21JC1404400] ; Shanghai Sailing Program[21YF1440700] ; NATCM's Project of High-level Construction of Key TCM Disciplines[ZYYZDXK-2023070] ; EMBO long-term fellowship[ALTF137-2019] ; Marie Sklodowska Curie individual fellowship[GABAARComp-897707] ; UK Medical Research Council[MC_UP_1201/15] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001336278700011 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313987]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Jiqiu; Wang, Weiqing |
| 作者单位 | 1.MRC Lab Mol Biol, Cambridge, England 2.Univ Paris, Inst Pasteur, Neural Circuits Spatial Nav & Memory, Paris, France 3.Chinese Acad Sci, Shanghai Inst Mat Med, Chinese Natl Ctr Drug Screening, Shanghai, Peoples R China 4.SJTUSM, Dept Anat & Physiol, Shanghai, Peoples R China 5.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 6.SJTUSM, Ruijin Hosp Luwan Branch, Clin Neurosci Ctr, Luwan Branch, Shanghai, Peoples R China 7.SJTUSM, Shanghai Natl Clin Res Ctr Metab Dis, Shanghai Natl Ctr Translat Med,Ruijin Hosp, Key Lab Endocrine & Metab Dis,Natl Hlth Commiss, Shanghai, Peoples R China 8.Shanghai Jiao Tong Univ Sch Med SJTUSM, Ruijin Hosp, Shanghai Inst Endocrine & Metab Dis, Dept Endocrine & Metab Dis, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lyu, Qianqian,Xue, Wenzhi,Liu, Ruixin,et al. A brain-to-gut signal controls intestinal fat absorption[J]. NATURE,2024:27. |
| APA | Lyu, Qianqian.,Xue, Wenzhi.,Liu, Ruixin.,Ma, Qinyun.,Kasaragod, Vikram Babu.,...&Wang, Weiqing.(2024).A brain-to-gut signal controls intestinal fat absorption.NATURE,27. |
| MLA | Lyu, Qianqian,et al."A brain-to-gut signal controls intestinal fat absorption".NATURE (2024):27. |
入库方式： OAI收割
来源：上海药物研究所
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