气候变化领域集成服务门户(CCPortal): Restriction of food intake by PPP1R17-expressing neurons in the DMH

CCPortal

DOI	10.1073/pnas.2100194118
	Restriction of food intake by PPP1R17-expressing neurons in the DMH
	Caglar C.; Friedman J.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Leptin-deficient ob/ob mice eat voraciously, and their food intake is markedly reduced by leptin treatment. In order to identify potentially novel sites of leptin action, we used PhosphoTRAP to molecularly profile leptin-responsive neurons in the hypothalamus and brainstem. In addition to identifying several known leptin responsive populations, we found that neurons in the dorsomedial hypothalamus (DMH) of ob/ob mice expressing protein phosphatase 1 regulatory subunit 17 (PPP1R17) constitutively express cFos and that this is suppressed by leptin treatment. Because ob mice are hyperphagic, we hypothesized that activating PPP1R17 neurons would increase food intake. However, chemogenetic activation of PPP1R17 neurons decreased food intake and body weight of ob/ob mice while inhibition of PPP1R17 neurons increased them. Similarly, in a scheduled feeding protocol that elicits increased consumption, mice also ate more when PPP1R17 neurons were inhibited and ate less when they were activated. Finally, we found that pair-feeding of ob mice reduced cFos expression to a similar extent as leptin and that reducing the amount of food available during scheduled feeding in DMHPpp1r17 neurons also decreased cFos in DMHPpp1r17 neurons. Finally, these neurons do not express the leptin receptor, suggesting that the effect of leptin on these neurons is indirect and secondary to reduced food intake. In aggregate, these results show that PPP1R17 neurons in the DMH are activated by increased food intake and in turn restrict intake to limit overconsumption, suggesting that they function to constrain binges of eating. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Body weight; DMH; Food intake; Leptin; Metabolism
语种	英语
scopus关键词	corticotropin releasing factor; leptin; phosphoprotein phosphatase; protein c fos; protein phosphatase 1 regulatory subunit 17; protein S6; tryptophan hydroxylase 2; unclassified drug; animal cell; animal experiment; animal tissue; Article; binge eating disorder; body weight; cell activation; controlled study; diet restriction; dorsomedial hypothalamic nucleus; food intake; hyperphagia; immunoprecipitation; male; mouse; nonhuman; ob/ob mouse; priority journal; protein expression; real time polymerase chain reaction; RNA sequencing; transcriptomics
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/180062
作者单位	HHMI, The Rockefeller University, New York, NY 10065, United States; Laboratory of Molecular Genetics, The Rockefeller University, New York, NY 10065, United States
推荐引用方式 GB/T 7714	Caglar C.,Friedman J.. Restriction of food intake by PPP1R17-expressing neurons in the DMH[J],2021,118(13).
APA	Caglar C.,&Friedman J..(2021).Restriction of food intake by PPP1R17-expressing neurons in the DMH.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Caglar C.,et al."Restriction of food intake by PPP1R17-expressing neurons in the DMH".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).