[1] MORTON G J,CUMMINGS D E,BASKIN D G,et al.Central nervous system control of food intake and body weight[J].Nature,2006,443(7109):289-295.

[2] CUMMINGS D E,OVERDUIN J.Gastrointestinal regulation of food intake[J].Journal of Clinical Investigation,2007,117:13-23.
[3] COTA D,PROULX K,BLAKE SMITH K A,et al.Hypothalamic mTOR signaling regulates food intake[J].Science,2006,312:927-930.
[4] WOODS S C,SEELEY R J,COTA D.Regulation of food intake through hypothalamic signaling networks involving mTOR[J].Annual Reviews,2008,28:295-311.
[5] HAO S Z,SHARP J W,ROSS-INTA C M,et al.Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex[J].Science,2005,307:1776-1778.
[6] GIETZEN D W,HAO S Z,ANTHONY T G,et al.Mechanisms of food intake repression in indispensable amino acid deficiency[J].Annual Review of Nutrition,2007,27:63-78.
[7] BLEVINS J E,SCHWARTZ M W,BASKIN D G.Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brainstem nuclei controlling meal size[J].American Journal of Physiology Regulatory,Integrative and Comparative Physiology,2004,287:R87-R96.
[8] KELLEY A E,BALDO B A,PRATT W E,et al.Corticostriatal-hypothalamic circuitry and food motivation:integration of energy,action and reward[J].Physiology & Behavior,2005,86:773-795.
[9] KELLEY A E,BERRIDGE K C.The neuroscience of natural rewards:relevance to addictive drugs[J].The Journal of Neuroscience,2002,22:3306-3311.
[10] GERAEDTS M C P,TTOOST F J,SARIS W H M.Gastrointestinal targets to modulate satiety and food intake[J].Obesity Reviews,2010,12:470-477.
[11] KARHUNEN L J,JUVONEN K R,HUOTARI A,et al.Effect of protein,fat,carbohydrate and fibre on gastrointestinal peptide release in humans[J].Regulatory Peptides,2008,149:70-78.
[12] HAHN T M,BREININGER J F,BASKIN D G,et al.Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons[J].Nature Neuroscience,1998,1:271-272.
[13] LUQUET S,PEREZ F A,HNASKO T S,et al.NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates[J].Science,2005,310(5748):683-685.

[14] CONE R D.Anatomy and regulation of the central melanocortin system[J].Nature Neuroscience,2005,8:571-578.
[15] FAN W,BOSTON B A,KESTERSON R A,et al.Role of melanocortinergic neurons in feeding and the agouti obesity syndrome[J].Nature,1997,385:165-168.
[16] PORTE D Jr.,BASKIN D G,SCHWARTZ M W.Leptin and insulin action in the central nervous system[J].Nutrition Reviews,2003,60:S20-S29.
[17] MURPHY K G,DHILLO W S,BLOOM S R.Gut peptides in the regulation of food intake and energy homeostasis[J].Endocrine Reviews,2006,27(7):719-727.
[18] SUZUKI K,SIMPSON K A,MINNION J S,et al.The role of gut hormones and the hypothalamus in appetite regulation[J].Endocrine Journal,2010,57(5):359-372.

[19] VAN DEN HEIDE L P,RAMAKERS M J,SMIDT M P.Insulin signaling in the central nervous system:learning to survive[J].Progress in Neurobiology,2006,79:205-221.
[20] PARDRIDGE W M,EISENBERG J,YANG J.Human blood-brain barrier insulin receptor[J].Journal of Neurochemistry,1985,44:1771-1778.
[21] HAVEL P J.Peripheral signals conveying metabolic information to the brain:short-term and long-term regulation of food intake and energy homeostasis[J].Experimental Biology and Medicine,2001,226(11):963-977.
[22] SEAQUIST E R,DAMBERG G S,TKAC I,et al.The effect of insulin on
in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans[J].Diabetes,2001,50(10):2203-2209.

[23] AIR E L,BENOIT S C,BLAKE SMITH K A,et al.Acute third ventricular administration of insulin decreases food intake in two paradigms[J].Pharmacology Biochemistry and Behavior,2002,72:423-429.
[24] OBICI S,FENG Z H,KARKANIAS G,et al.Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats[J].Nature Neuroscience,2002,5:566-572.
[25] FLIER J S.Obesity wars:molecular progress confronts an expanding epidemic[J].Cell,2004,116:337-350.
[26] HAVEL P J,OWNSEND R,CHAUMP L,et al.High-fat meals reduce 24-h circulating leptin concentrations in women[J].Diabetes,1999,48:334-341.
[27] KORBONITS M,TRAINER P J,LITTLE J A,et al.Leptin levels do not change acutely with food administration in normal or obese subjects,but are negatively correlated with pituitary-adrenal activity[J].Clinical Endocrinology,1997,46:751-757.
[28] BANKS W A,KASTIN A J,HUANG W,et al.Leptin enters the brain by a saturable system independent of insulin[J].Peptides,1996,17:305-311.
[29] FEI H,OKANO H J,LI C,et al.Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues[J].Proceedings of the National Academy of Sciences of the United States of America,1997,94:7001-7005.
[30] CHEN H,CHARLAT O,TARTAGLIA L A,et al.Evidence that the diabetes gene encodes the leptin receptor:identification of a mutation in the leptin receptor gene in db/db mice[J].Cell,1996,84:491-495.
[31] SCHWARTZ M W,WOODS S C,PORTE D,et al.Central nervous system control of food intake[J].Nature,2000,404:661-671.
[32] LENARD N R,BERTHOUD H.Central and peripheral regulation of food intake and physical activity:pathways and genes[J].Obesity,2008,16:S11-S22.
[33] OBICI S,FENG Z H,MORGAN K,et al.Central administration of oleic acid inhibits glucose production and food intake[J].Diabetes,2002,51:271-275.
[34] HARDIE D G,CARLING D.The AMP-activated protein kinase-fuel gauge of the mammalian cell?[J].European Journal of Biochemistry,1997,246:259-273.
[35] WULLSCHLEGER S,LOEWITH R,HALL M N.TOR signaling in growth and metabolism[J].Cell,2006,124:471-484.
[36] MINOKOSHI Y,ALQUIER T,FURUKAWA N,et al.AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus[J].Nature,2004,428:569-574.
[37] XUE B Z,KAHN B B.AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues[J].The Journal of Physiology,2006,574(1):73-83.

[38] MORRISON C D,XI X C,WHITE C L,et al.Amino acids inhibit
Agrp gene expression via an mTOR-dependent mechanism[J].American Journal of Physiology Endocrinology and Metabolism,2007,293:E165-E171.
[39] ZONCU R,EFEYAN A,SABATINI D M.mTOR:from growth signal integration to cancer,diabetes and ageing[J].Nature Reviews Molecular Cell Biology,2011,12:21-35.
[40] LAPLANTE M,SABATINI D W.mTOR signaling in growth control and disease[J].Cell,2012,149:274-293.
[41] COTA D,MATTER E K,WOODS S C,et al.The role of hypothalamic mammalian target of rapamycin complex 1 signaling in diet induced obesity[J].The Journal of Neuroscience,2008,28(28):7202-7208.

[42] WU Q,ZHANG Y,XU J,et al.Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in
Drosophila[J].Proceedings of the National Academy of Sciences of the United States of America,2005,102:13289-13294.
[43] DAGON Y,HUR E,ZHENG B,et al.p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake[J].Cell Metabolism,2012,16:104-112.
[44] SHARP J W,ROSS-INTA C M,HAO S Z,et al.Co-localization of phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2) and phosphorylated eukaryotic initiation factor 2α (eIF2α) in response to a threonine-devoid diet[J].Journal of Comparative Neurology,2006,494:485-494.
[45] SOOD R,PORTER A C,OLSEN D,et al.A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2α[J].Genetics,2000,154:787-801.
[46] ZHANG P,MCGRATH BC,REINERT J,et al.The GCN2 eIF2α kinase is required for adaptation to amino acid deprivation in mice[J].Molecular and Cellular Biology,2002,22:6681-6688.
[47] DONG J S,QIU H F,GARCIA-BARRIO M,et al.Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain[J].Molecular Cell,2000,6:269-279.
[48] BLAIS A,HUNEAU J F,MAGRUM L J,et al.Threonine deprivation rapidly activates the system A amino acid transporter in primary cultures of rat neurons from the essential amino acid sensor in the anterior piriform cortex[J].The Journal of Nutrition,2003,133:2156-2164.
[49] HUTSON S M,LIETH E,LANOUE K F.Function of leucine in excitatory neurotransmitter metabolism in the central nervous system[J].The Journal of Nutrition,2001,131:846S-850S.
[50] SHARP J W,ROSS C M,KOEHNLE T J,et al.Phosphorylation of Ca
2+/calmodulin dependent protein kinase type II and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor in response to a threonine-devoid diet[J].Neuroscience,2004,126:1053-62.
[51] WEK R C,JIANG H Y,ANTHONY T G.Coping with stress:eIF2 kinases and translational control[J].Biochemical Society Transactions,2006,34:7-11.
[52] KITAMURA T,FENG Y,KITAMURA1 Y I,et al.Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake[J].Nature Medicine,2006,12:534-540.
[53] PLUM L,BELGARDT B F,BRUNING J C.Central insulin action in energy and glucose homeostasis[J].Journal of Clinical Investigation,2006,116:1761-66.
[54] BATES S H,STEARNS W H,DUNDON T A,et al.STAT3 signalling is required for leptin regulation of energy balance but not reproduction[J].Nature,2003,421:856-859.