气候变化领域集成服务门户(CCPortal): GFRAL-expressing neurons suppress food intake via aversive pathways

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DOI	10.1073/pnas.2021357118
	GFRAL-expressing neurons suppress food intake via aversive pathways
	Sabatini P.V.; Frikke-Schmidt H.; Arthurs J.; Gordian D.; Patel A.; Rupp A.C.; Adams J.M.; Wang J.; Jørgensen S.B.; Olson D.P.; Palmiter R.D.; Myers M.G.; Jr.; Seeley R.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	The TGFβ cytokine family member, GDF-15, reduces food intake and body weight and represents a potential treatment for obesity. Because the brainstem-restricted expression pattern of its receptor, GDNF Family Receptor α–like (GFRAL), presents an exciting opportunity to understand mechanisms of action for area postrema neurons in food intake; we generated GfralCre and conditional GfralCreERT mice to visualize and manipulate GFRAL neurons. We found infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons. TRAP-Seq analysis of GFRAL neurons revealed their expression of a wide range of neurotransmitters and neuropeptides. Artificially activating GfralCre-expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). GFRAL neurons most strongly innervate the parabrachial nucleus (PBN), where they target CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non–meal-associated pathophysiologic signals to suppress nutrient uptake and absorption. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Area postrema; CGRP; GDF-15; GFRAL; Obesity
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180543
作者单位	Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, United States; Department of Surgery, University of Michigan, Ann Arbor, MI 48109, United States; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98115, United States; Howard Hughes Medical Institute, Department of Genome Sciences, University of Washington, Seattle, WA 98115, United States; Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, United States; School of Biological Sciences, Illinois State University, Normal, IL 61790, United States; College of Medical Science, China Three Gorges University, Yichang, 43002, China; Diabetes Research Unit, Novo Nordisk A/S, Maaloev, 2760, Denmark
推荐引用方式 GB/T 7714	Sabatini P.V.,Frikke-Schmidt H.,Arthurs J.,et al. GFRAL-expressing neurons suppress food intake via aversive pathways[J],2021,118(8).
APA	Sabatini P.V..,Frikke-Schmidt H..,Arthurs J..,Gordian D..,Patel A..,...&Seeley R.J..(2021).GFRAL-expressing neurons suppress food intake via aversive pathways.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Sabatini P.V.,et al."GFRAL-expressing neurons suppress food intake via aversive pathways".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).