mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior

被引：18
作者：
Albert, Verena [1 ]
Cornu, Marion [1 ]
Hall, Michael N. [1 ]
机构：
[1] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 464卷 / 02期
基金：
瑞士国家科学基金会;
关键词：
mTORC1; Raptor; Hypothalamus; Agrp; NPY; Metabolism; HYPOTHALAMIC DYSFUNCTION; APPETITE REGULATION; NEUROPEPTIDE-Y; OBESITY; ENERGY; MICE; DEFICIENCY; METABOLISM; ACTIVATION; GHRELIN;
D O I：
10.1016/j.bbrc.2015.06.161
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Orexigenic agouti-related protein/neuropeptide Y (Agrp/NPY) neurons and an orexigenic proopiomelanocortin (POMC) neurons of the hypothalamus regulate feeding behavior and energy homeostasis. An understanding of the molecular signaling pathways that regulate Agrp/NPY and POMC function could lead to novel treatments for metabolic disorders. Target of Rapamycin Complex 1 (TORC1) is a nutrient-activated protein kinase and central controller of growth and metabolism. We therefore investigated the role of mammalian TORC1 (mTORC1) in Agrp neurons. We generated and characterized Agrp neuron-specific raptor knockout (Agrp-raptor MO) mice. Agrp-raptor KO mice displayed reduced, non-circadian expression of Agrp and NPY but normal feeding behavior and energy homeostasis on both normal and high fat diet. Thus, mTORC1 in Agrp neurons controls circadian expression of orexigenic neuropeptides but is dispensable for the regulation of feeding behavior and energy metabolism. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码：480 / 486
页数：7
相关论文
共 37 条
[1]   mTOR signaling in cellular and organismal energetics [J].
Albert, Verena ;
Hall, Michael N. .
CURRENT OPINION IN CELL BIOLOGY, 2015, 33 :55-66
[2]   Role of neuropeptides in appetite regulation and obesity - A review [J].
Arora, Sarika ;
Anubhuti .
NEUROPEPTIDES, 2006, 40 (06) :375-401
[3]   Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy [J].
Bentzinger, C. Florian ;
Romanino, Klaas ;
Cloetta, Dimitri ;
Lin, Shuo ;
Mascarenhas, Joseph B. ;
Oliveri, Filippo ;
Xia, Jinyu ;
Casanova, Emilio ;
Costa, Celine F. ;
Brink, Marijke ;
Zorzato, Francesco ;
Hall, Michael N. ;
Rueegg, Markus A. .
CELL METABOLISM, 2008, 8 (05) :411-424
[4]   CIRCADIAN REGULATION OF MAMMALIAN TARGET OF RAPAMYCIN SIGNALING IN THE MOUSE SUPRACHIASMATIC NUCLEUS [J].
Cao, R. ;
Anderson, F. E. ;
Jung, Y. -J. ;
Dziema, H. ;
Obrietan, K. .
NEUROSCIENCE, 2011, 181 :79-88
[5]   The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis [J].
Cone, RD ;
Cowley, MA ;
Butler, AA ;
Fan, W ;
Marks, DL ;
Low, MJ .
INTERNATIONAL JOURNAL OF OBESITY, 2001, 25 (Suppl 5) :S63-S67
[6]   Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21 [J].
Cornu, Marion ;
Oppliger, Wolfgang ;
Albert, Verena ;
Robitaille, Aaron M. ;
Trapani, Francesca ;
Quagliata, Luca ;
Fuhrer, Tobias ;
Sauer, Uwe ;
Terracciano, Luigi ;
Hall, Michael N. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (32) :11592-11599
[7]   Hypothalamic mTOR signaling regulates food intake [J].
Cota, D ;
Proulx, K ;
Smith, KAB ;
Kozma, SC ;
Thomas, G ;
Woods, SC ;
Seeley, RJ .
SCIENCE, 2006, 312 (5775) :927-930
[8]   mTOR signaling in disease [J].
Dazert, Eva ;
Hall, Michael N. .
CURRENT OPINION IN CELL BIOLOGY, 2011, 23 (06) :744-755
[9]   Signal integration by mTORC1 coordinates nutrient input with biosynthetic output [J].
Dibble, Christian C. ;
Manning, Brendan D. .
NATURE CELL BIOLOGY, 2013, 15 (06) :555-564
[10]   Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y [J].
Erickson, JC ;
Clegg, KE ;
Palmiter, RD .
NATURE, 1996, 381 (6581) :415-418
1234