Yamada’s Textbook of Gastroenterology

Sixth Edition

Edited by Daniel K. Podolsky,
Michael Camilleri, J. Gregory Fitz,
Anthony N. Kalloo, Fergus Shanahan, Timothy C. Wang

References

Control of appetite/satiety and energy balance

1. VoelkerR. Escalating obesity rates pose health, budget threats. JAMA[News]. 2012;308:1514. CrossRef

2. HetheringtonAW, RansonSW. Hypothalamic lesions and adiposity in the rat. Anat Rec1940;78:149. CrossRef

3. WilliamsKW, ElmquistJK. From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2012;15:1350. CrossRef

4. ZhangY, ProencaR, MaffeiM, et al.Positional cloning of the mouse obese gene and its human homologue. Nature1994;372:425. CrossRef

5. FanW, BostonBA, KestersonRA, et al.Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 1997;385:165. CrossRef

6. ConeRD, LuD, KoppulaS, et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog Horm Res[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review]. 1996;51:287, discussion 8.

7. MountjoyKG, MortrudMT, LowMJ, et al.Localization of the melanocortin‐4 receptor (MC4‐R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol[Research Support, U.S. Gov't, P.H.S.]. 1994;8:1298.

8. MagenisRE, SmithL, NadeauJH, et al.Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human. Mamm Genome[Comparative Study Research Support, U.S. Gov't, P.H.S.]. 1994;5:503. CrossRef

9. Roselli‐RehfussL, MountjoyKG, RobbinsLS, et al.Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci U S A[Comparative Study]. 1993;90:8856. CrossRef

10. MountjoyKG, RobbinsLS, MortrudMT, et al.The cloning of a family of genes that encode the melanocortin receptors. Science[Research Support, U.S. Gov't, P.H.S.]. 1992;257:1248. CrossRef

11. PocaiA, ObiciS, SchwartzGJ, et al.A brain‐liver circuit regulates glucose homeostasis. Cell Metab2005;1:53. CrossRef

12. GautronL, ElmquistJK. Sixteen years and counting: an update on leptin in energy balance. J Clin Invest[Research Support, Non‐U.S. Gov't Review]. 2011;121:2087. CrossRef

13. SohnJW, XuY, JonesJE, et al.Serotonin 2C receptor activates a distinct population of arcuate pro‐opiomelanocortin neurons via TRPC channels. Neuron[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2011;71:488. CrossRef

14. AhimaRS, PrabakaranD, MantzorosC, et al.Role of leptin in the neuroendocrine response to fasting. Nature1996;382:250. CrossRef

15. AhimaRS, SaperCB, FlierJS, et al.Leptin regulation of neuroendocrine systems. Front Neuroendocrinol2000;21:263. CrossRef

16. FlierJS. Obesity wars: molecular progress confronts an expanding epidemic. Cell2004;116:337. CrossRef

17. KolaczynskiJW, OhannesianJP, ConsidineRV, et al.Response of leptin to short‐term and prolonged overfeeding in humans. J Clin Endocrinol Metab1996;81:4162.

18. SinhaMK, OhannesianJP, HeimanML, et al.Nocturnal rise of leptin in lean, obese, and non‐insulin‐dependent diabetes mellitus subjects. J Clin Invest1996;97:1344. CrossRef

19. SinhaMK, OpentanovaI, OhannesianJP, et al.Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short‐term fasting. J Clin Invest1996;98:1277. CrossRef

20. FrederichRC, HamannA, AndersonS, et al.Leptin levels reflect body lipid content in mice: evidence for diet‐induced resistance to leptin action. Nat Med[Research Support, U.S. Gov't, P.H.S.]. 1995;1:1311. CrossRef

21. MaffeiM, HalaasJ, RavussinE, et al.Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight‐reduced subjects. Nat Med1995;1:1155. CrossRef

22. RosenbaumM, NicolsonM, HirschJ, et al.Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab1996;81:3424.

23. BarshGS, FarooqiIS, O'RahillyS. Genetics of body‐weight regulation. Nature2000;404:644.

24. FarooqiIS. Monogenic human obesity syndromes. Prog Brain Res2006;153:119. CrossRef

25. FarooqiIS, JebbSA, LangmackG, et al.Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med1999;341:879. CrossRef

26. GalganiJE, GreenwayFL, CaglayanS, et al.Leptin replacement prevents weight loss‐induced metabolic adaptation in congenital leptin‐deficient patients. J Clin Endocrinol Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;95:851. CrossRef

27. LicinioJ, CaglayanS, OzataM, et al.Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin‐deficient adults. Proc Natl Acad Sci U S A[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2004;101:4531. CrossRef

28. OzataM, OzdemirIC, LicinioJ. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin‐mediated defects. J Clin Endocrinol Metab1999;84:3686. CrossRef

29. FarooqiIS, MatareseG, LordGM, et al.Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest[Case Reports Research Support, Non‐U.S. Gov't]. 2002;110:1093. CrossRef

30. CampfieldLA, SmithFJ, GuisezY, et al.Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science1995;269:546. CrossRef

31. ChuaSCJr, ChungWK, Wu‐PengXS, et al.Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science1996;271:994. CrossRef

32. HalaasJL, GajiwalaKS, MaffeiM, et al.Weight‐reducing effects of the plasma protein encoded by the obese gene. Science1995;269:543. CrossRef

33. PelleymounterMA, CullenMJ, BakerMB, et al.Effects of the obese gene product on body weight regulation in ob/ob mice. Science1995;269:540. CrossRef

34. FarooqiIS, O'RahillyS. Leptin: a pivotal regulator of human energy homeostasis. Am J Clin Nutr[Review]. 2009;89:980S. CrossRef

35. BaicyK, LondonED, MonterossoJ, et al.Leptin replacement alters brain response to food cues in genetically leptin‐deficient adults. Proc Natl Acad Sci U S A[Research Support, N.I.H., Extramural]. 2007;104:18276. CrossRef

36. LicinioJ, RibeiroL, BusnelloJV, et al.Effects of leptin replacement on macro‐ and micronutrient preferences. Int J Obes[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2007;31:1859. CrossRef

37. CaroJF, KolaczynskiJW, NyceMR, et al.Decreased cerebrospinal‐fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet1996;348:159. CrossRef

38. HouseknechtKL, MantzorosCS, KuliawatR, et al.Evidence for leptin binding to proteins in serum of rodents and humans: modulation with obesity. Diabetes1996;45:1638. CrossRef

39. BjorbaekC, ElmquistJK, FrantzJD, et al.Identification of SOCS‐3 as a potential mediator of central leptin resistance. Mol Cell1998;1:619. CrossRef

40. BjorbaekC, El‐HaschimiK, FrantzJD, et al.The role of SOCS‐3 in leptin signaling and leptin resistance. J Biol Chem1999;274:30059. CrossRef

41. SpiegelmanBM, FlierJS. Obesity and the Regulation of Energy Balance. Cell2001;104:531. CrossRef

42. El‐HaschimiK, PierrozDD, HilemanSM, et al.Two defects contribute to hypothalamic leptin resistance in mice with diet‐induced obesity. J Clin Invest2000;105:1827. CrossRef

43. MunzbergH, BjornholmM, BatesSH, et al.Leptin receptor action and mechanisms of leptin resistance. Cell Mol Life Sci[Review]. 2005;62:642. CrossRef

44. MarkAL. Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol2013;305:R566. CrossRef

45. HeymsfieldSB, GreenbergAS, FujiokaK, et al.Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose‐escalation trial. JAMA1999;282:1568. CrossRef

46. FarooqiIS, WangensteenT, CollinsS, et al.Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med[Research Support, Non‐U.S. Gov't]. 2007;356:237. CrossRef

47. KimberW, PeelmanF, PrieurX, et al.Functional characterization of naturally occurring pathogenic mutations in the human leptin receptor. Endocrinology[Research Support, Non‐U.S. Gov't]. 2008;149:6043. CrossRef

48. FarooqiIS, O'RahillyS. Monogenic obesity in humans. Annu Rev Med[Review]. 2005;56:443. CrossRef

49. ClementK, VaisseC, LahlouN, et al.A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature1998;392:398. CrossRef

50. ColemanDL. Obese and diabetes: two mutant genes causing diabetes‐obesity syndromes in mice. Diabetologia1978;14:141. CrossRef

51. ColemanDL. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia1973;9:294. CrossRef

52. ColemanDL, HummelKP. Effects of parabiosis of normal with genetically diabetic mice. Am J Physiol1969;217:1298.

53. BaumannH, MorellaKK, WhiteDW, et al.The full‐length leptin receptor has signaling capabilities of interleukin 6‐type cytokine receptors. Proc Natl Acad Sci U S A1996;93:8374. CrossRef

54. TartagliaLA. The leptin receptor. J Biol Chem1997;272:6093. CrossRef

55. TartagliaLA, DembskiM, WengX, et al.Identification and expression cloning of a leptin receptor, OB‐R. Cell1995;83:1263. CrossRef

56. LeeGH, ProencaR, MontezJM, et al.Abnormal splicing of the leptin receptor in diabetic mice. Nature1996;379:632. CrossRef

57. BjorbaekC, KahnBB. Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review]. 2004;59:305. CrossRef

58. MyersMGJr, MunzbergH, LeinningerGM, et al.The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2009;9:117. CrossRef

59. MyersMGJr, OlsonDP. Central nervous system control of metabolism. Nature[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2012;491:357. CrossRef

60. HillJW, WilliamsKW, YeC, et al.Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest2008;118:1796. CrossRef

61. NiswenderKD, MortonGJ, StearnsWH, et al.Intracellular signalling. Key enzyme in leptin‐induced anorexia. Nature2001;413:794. CrossRef

62. Al‐QassabH, SmithMA, IrvineEE, et al.Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab[Research Support, Non‐U.S. Gov't]. 2009;10:343. CrossRef

63. BatesSH, DundonTA, SeifertM, et al.LRb‐STAT3 signaling is required for the neuroendocrine regulation of energy expenditure by leptin. Diabetes[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2004;53:3067. CrossRef

64. BatesSH, KulkarniRN, SeifertM, et al.Roles for leptin receptor/STAT3‐dependent and ‐independent signals in the regulation of glucose homeostasis. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2005;1:169. CrossRef

65. BatesSH, StearnsWH, DundonTA, et al.STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature2003;421:856. CrossRef

66. BuettnerC, PocaiA, MuseED, et al.Critical role of STAT3 in leptin's metabolic actions. Cell Metab2006;4:49. CrossRef

67. CowleyMA, SmartJL, RubinsteinM, et al.Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature2001;411:480. CrossRef

68. SpanswickD, SmithMA, GroppiVE, et al.Leptin inhibits hypothalamic neurons by activation of ATP‐sensitive potassium channels. Nature1997;390:521. CrossRef

69. SpanswickD, SmithMA, MirshamsiS, et al.Insulin activates ATP‐sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci2000;3:757. CrossRef

70. WilliamsKW, SmithBN. Rapid inhibition of neural excitability in the nucleus tractus solitarii by leptin: implications for ingestive behaviour. J Physiol2006;573(Pt 2):395. CrossRef

71. SohnJW, ElmquistJK, WilliamsKW. Neuronal circuits that regulate feeding behavior and metabolism. Trends Neurosci2013;36:504. CrossRef

72. PlumL, MaX, HampelB, et al.Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet‐sensitive obesity. J Clin Invest[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2006;116:1886. CrossRef

73. PlumL, RotherE, MunzbergH, et al.Enhanced leptin‐stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation. Cell Metab[Research Support, Non‐U.S. Gov't]. 2007;6:431. CrossRef

74. RoseberryAG, LiuH, JacksonAC, et al.Neuropeptide Y‐Mediated Inhibition of Proopiomelanocortin Neurons in the Arcuate Nucleus Shows Enhanced Desensitization in ob/ob Mice. Neuron2004;41:711. CrossRef

75. CohenP, ZhaoC, CaiX, et al.Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest2001;108:1113. CrossRef

76. CoppariR, IchinoseM, LeeCE, et al.The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metab2005;1:63. CrossRef

77. MortonGJ, BlevinsJE, WilliamsDL, et al.Leptin action in the forebrain regulates the hindbrain response to satiety signals. J Clin Invest[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2005;115:703. CrossRef

78. MortonGJ, GellingRW, NiswenderKD, et al.Leptin regulates insulin sensitivity via phosphatidylinositol‐3‐OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab2005;2:411. CrossRef

79. MortonGJ, NiswenderKD, RhodesCJ, et al.Arcuate nucleus‐specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats. Endocrinology2003;144:2016. CrossRef

80. BerglundED, ViannaCR, DonatoJJr, et al.Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest[Research Support, N.I.H., Extramural]. 2012;122:1000. CrossRef

81. ZigmanJM, ElmquistJK. Minireview: from anorexia to obesity–the yin and yang of body weight control. Endocrinology2003;144:3749. CrossRef

82. ElmquistJK, CoppariR, BalthasarN, et al.Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol2005;493:63. CrossRef

83. SohnJW, ElmquistJK, WilliamsKW. Neuronal circuits that regulate feeding behavior and metabolism. Trends Neurosci2013;●●:●●.

84. WeigleDS, DuellPB, ConnorWE, et al.Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab1997;82:561.

85. FarooqiIS, BullmoreE, KeoghJ, et al.Leptin regulates striatal regions and human eating behavior. Science[Case Reports Clinical Trial Research Support, Non‐U.S. Gov't]. 2007;317:1355. CrossRef

86. FiglewiczDP, NaleidAM, SipolsAJ. Modulation of food reward by adiposity signals. Physiol Behav2006;●●:●●.

87. FultonS, PissiosP, ManchonRP, et al.Leptin regulation of the mesoaccumbens dopamine pathway. Neuron2006;51:811. CrossRef

88. FultonS, WoodsideB, ShizgalP. Modulation of brain reward circuitry by leptin. Science2000;287:125. CrossRef

89. HommelJD, TrinkoR, SearsRM, et al.Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron2006;51:801. CrossRef

90. GrillHJ, SkibickaKP, HayesMR. Imaging obesity: fMRI, food reward, and feeding. Cell Metab[Comment].2007;6:423. CrossRef

91. WangL, BarachinaMD, MartinezV, et al.Synergistic interaction between CCK and leptin to regulate food intake. Regul Pept[Research Support, U.S. Gov't, P.H.S. Review]. 2000;92:79. CrossRef

92. MartinezV, BarrachinaMD, WangL, et al.Intracerebroventricular leptin inhibits gastric emptying of a solid nutrient meal in rats. Neuroreport[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 1999;10:3217. CrossRef

93. BarrachinaMD, MartinezV, WangL, et al.Synergistic interaction between leptin and cholecystokinin to reduce short‐term food intake in lean mice. Proc Natl Acad Sci U S A[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 1997;94:10455. CrossRef

94. BarrachinaMD, MartinezV, WeiJY, et al.Leptin‐induced decrease in food intake is not associated with changes in gastric emptying in lean mice. Am J Physiol[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 1997;272(3 Pt 2):R1007.

95. GrillHJ, HayesMR. Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance. Cell Metab[Research Support, N.I.H., Extramural Review]. 2012;16:296. CrossRef

96. GrillHJ, KaplanJM. The neuroanatomical axis for control of energy balance. Front Neuroendocrinol2002;23:2. CrossRef

97. JacobRJ, DziuraJ, MedwickMB, et al.The effect of leptin is enhanced by microinjection into the ventromedial hypothalamus. Diabetes1997;46:150. CrossRef

98. LeinningerGM, JoYH, LeshanRL, et al.Leptin acts via leptin receptor‐expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2009;10:89. CrossRef

99. LeinningerGM, MyersMGJr. LRb signals act within a distributed network of leptin‐responsive neurones to mediate leptin action. Acta Physiol (Oxf)[Review].2008;192:49. CrossRef

100. LeinningerGM, OplandDM, JoYH, et al.Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2011;14:313. CrossRef

101. SatohN, OgawaY, KatsuuraG, et al.Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)‐lesioned rats: evidence for loss of its satiety effect in VMH‐lesioned rats. Endocrinology1997;138:947.

102. SchwartzMW, WoodsSC, PorteDJr, et al.Central nervous system control of food intake. Nature2000;404:661.

103. SaperCB, ChouTC, ElmquistJK. The need to feed: homeostatic and hedonic control of eating. Neuron2002;36:199. CrossRef

104. KojimaM, HosodaH, DateY, et al.Ghrelin is a growth‐hormone‐releasing acylated peptide from stomach. Nature1999;402:656. CrossRef

105. DateY, KojimaM, HosodaH, et al.Ghrelin, a novel growth hormone‐releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology[Research Support, Non‐U.S. Gov't]. 2000;141:4255.

106. RindiG, NecchiV, SavioA, et al.Characterisation of gastric ghrelin cells in man and other mammals: studies in adult and fetal tissues. Histochem Cell Biol[Research Support, Non‐U.S. Gov't]. 2002;117:511. CrossRef

107. SakataI, NakanoY, Osborne‐LawrenceS, et al.Characterization of a novel ghrelin cell reporter mouse. Regul Pept[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2009;155:91. CrossRef

108. HosodaH, KojimaM, MatsuoH, et al.Ghrelin and des‐acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun[Research Support, Non‐U.S. Gov't]. 2000;279:909. CrossRef

109. HosodaH, KojimaM, MizushimaT, et al.Structural divergence of human ghrelin. Identification of multiple ghrelin‐derived molecules produced by post‐translational processing. J Biol Chem[Research Support, Non‐U.S. Gov't]. 2003;278:64. CrossRef

110. YangJ, BrownMS, LiangG, et al.Identification of the acyltransferase that octanoylates ghrelin, an appetite‐stimulating peptide hormone. Cell2008;132:387. CrossRef

111. HowardAD, FeighnerSD, CullyDF, et al.A receptor in pituitary and hypothalamus that functions in growth hormone release. Science1996;273:974. CrossRef

112. MomanyFA, BowersCY, ReynoldsGA, et al.Conformational energy studies and in vitro and in vivo activity data on growth hormone‐releasing peptides. Endocrinology[Research Support, Non‐U.S. Gov't]. 1984;114:1531. CrossRef

113. BowersCY, MomanyF, ReynoldsGA, et al.Structure‐activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro. Endocrinology[In Vitro Research Support, U.S. Gov't, P.H.S.]. 1980;106:663. CrossRef

114. HorvathTL, DianoS, SotonyiP, et al.Minireview: ghrelin and the regulation of energy balance–a hypothalamic perspective. Endocrinology2001;142:4163.

115. CummingsDE, PurnellJQ, FrayoRS, et al.A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes2001;50:1714. CrossRef

116. CummingsDE, WeigleDS, FrayoRS, et al.Plasma ghrelin levels after diet‐induced weight loss or gastric bypass surgery. N Engl J Med2002;346:1623. CrossRef

117. TschopM, SmileyDL, HeimanML. Ghrelin induces adiposity in rodents. Nature2000;407:908. CrossRef

118. NakazatoM, MurakamiN, DateY, et al.A role for ghrelin in the central regulation of feeding. Nature2001;409:194. CrossRef

119. CummingsDE, FrayoRS, MarmonierC, et al.Plasma ghrelin levels and hunger scores among humans initiating meals voluntarily in the absence of time‐ and food‐related cues. Am J Physiol Endocrinol Metab2004;●●:●●.

120. FaulconbridgeLF, CummingsDE, KaplanJM, et al.Hyperphagic effects of brainstem ghrelin administration. Diabetes2003;52:2260. CrossRef

121. NagayaN, UematsuM, KojimaM, et al.Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation2001;104:2034. CrossRef

122. TolleV, KademM, Bluet‐PajotMT, et al.Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab2003;88:109. CrossRef

123. OttoB, CuntzU, FruehaufE, et al.Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol2001;145:669. CrossRef

124. CummingsDE, ClementK, PurnellJQ, et al.Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med2002;8:643. CrossRef

125. ThalerJP, CummingsDE. Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology[Review].2009;150:2518. CrossRef

126. HaqqAM, GrambowSC, MuehlbauerM, et al.Ghrelin concentrations in Prader‐Willi syndrome (PWS) infants and children: changes during development. Clin Endocrinol (Oxf)[Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non‐U.S. Gov't]. 2008;69:911. CrossRef

127. HaqqAM, StadlerDD, RosenfeldRG, et al.Circulating ghrelin levels are suppressed by meals and octreotide therapy in children with Prader‐Willi syndrome. J Clin Endocrinol Metab[Clinical Trial Research Support, U.S. Gov't, P.H.S.]. 2003;88:3573. CrossRef

128. EliasCF, LeeCE, KellyJF, et al.Characterization of CART neurons in the rat and human hypothalamus. J Comp Neurol2001, 432:1. CrossRef

129. EliasCF, SaperCB, Maratos‐FlierE, et al.Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol1998;402:442. CrossRef

130. ConeRD. Anatomy and regulation of the central melanocortin system. Nat Neurosci2005;8:571. CrossRef

131. WilliamsKW, ElmquistJK. Lighting up the hypothalamus: coordinated control of feeding behavior. Nat Neurosci[Comment News]. 2011;14:277. CrossRef

132. BrobergerC, De LeceaL, SutcliffeJG, et al.Hypocretin/orexin‐ and melanin‐concentrating hormone‐expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene‐related protein systems. J Comp Neurol1998;402:460. CrossRef

133. HahnTM, BreiningerJF, BaskinDG, et al.Coexpression of Agrp and NPY in fasting‐activated hypothalamic neurons. Nat Neurosci1998;1:271. CrossRef

134. GroppE, ShanabroughM, BorokE, et al.Agouti‐related peptide‐expressing neurons are mandatory for feeding. Nat Neurosci[Comparative Study Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2005;8:1289. CrossRef

135. LuquetS, PerezFA, HnaskoTS, et al.NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science2005;310:683. CrossRef

136. WuQ, BoyleMP, PalmiterRD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2009;137:1225. CrossRef

137. WuQ, HowellMP, CowleyMA, et al.Starvation after AgRP neuron ablation is independent of melanocortin signaling. Proc Natl Acad Sci U S A[Research Support, N.I.H., Extramural]. 2008;105:2687. CrossRef

138. KrashesMJ, KodaS, YeC, et al.Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2011;121:1424. CrossRef

139. AponteY, AtasoyD, SternsonSM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci[Research Support, Non‐U.S. Gov't]. 2011;14:351. CrossRef

140. AtasoyD, BetleyJN, SuHH, et al.Deconstruction of a neural circuit for hunger. Nature[Research Support, Non‐U.S. Gov't]. 2012;488:172. CrossRef

141. YangY, AtasoyD, SuHH, et al.Hunger states switch a flip‐flop memory circuit via a synaptic AMPK‐dependent positive feedback loop. Cell[Research Support, Non‐U.S. Gov't]. 2011;146:992. CrossRef

142. ZhengH, PattersonLM, RhodesCJ, et al.A potential role for hypothalamomedullary POMC projections in leptin‐induced suppression of food intake. Am J Physiol Regul Integr Comp Physiol[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;298:R720. CrossRef

143. van de WallE, LeshanR, XuAW, et al.Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology2008;149:1773. CrossRef

144. XuAW, Ste‐MarieL, KaelinCB, et al.Inactivation of Stat3 in Pomc neurons causes decreased Pomc expression, mild obesity and defects in compensatory refeeding. Endocrinology2006;●●:●●.

145. BalthasarN, CoppariR, McMinnJ, et al.Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron[Comparative Study Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2004;42:983. CrossRef

146. HillJW, EliasCF, FukudaM, et al.Direct insulin and leptin action on pro‐opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;11:286. CrossRef

147. ShiH, StraderAD, SorrellJE, et al.Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis. Am J Physiol Endocrinol Metab[Comparative Study Research Support, N.I.H., Extramural]. 2008;294:E630. CrossRef

148. GongL, YaoF, HockmanK, et al.Signal transducer and activator of transcription‐3 is required in hypothalamic agouti‐related protein/neuropeptide Y neurons for normal energy homeostasis. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2008;149:3346. CrossRef

149. HuoL, GamberK, GreeleyS, et al.Leptin‐dependent control of glucose balance and locomotor activity by POMC neurons. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2009;9:537. CrossRef

150. BostonBA, BlaydonKM, VarnerinJ, et al.Independent and additive effects of central POMC and leptin pathways on murine obesity. Science1997;278:1641. CrossRef

151. MarshDJ, HollopeterG, HuszarD, et al.Response of melanocortin‐4 receptor‐deficient mice to anorectic and orexigenic peptides. Nat Genet1999;21:119. CrossRef

152. DubucPU. Effects of limited food intake on the obese‐hyperglycemic syndrome. Am J Physiol[Comparative Study Research Support, U.S. Gov't, P.H.S.]. 1976;230:1474.

153. PocaiA, LamTK, Gutierrez‐JuarezR, et al.Hypothalamic K(ATP) channels control hepatic glucose production. Nature[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2005;434:1026. CrossRef

154. KamoharaS, BurcelinR, HalaasJL, et al.Acute stimulation of glucose metabolism in mice by leptin treatment. Nature1997;389:374. CrossRef

155. BarzilaiN, WangJ, MassilonD, et al.Leptin selectively decreases visceral adiposity and enhances insulin action. J Clin Invest[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 1997;100:3105. CrossRef

156. RossettiL, MassillonD, BarzilaiN, et al.Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J Biol Chem[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 1997;272:27758. CrossRef

157. HillJW, XuY, PreitnerF, et al.Phosphatidyl inositol 3‐kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2009;150:4874. CrossRef

158. Keen‐RhinehartE, KalraSP, KalraPS. Leptin‐receptor gene transfer into the arcuate nucleus of female fatty zucker rats using recombinant adeno‐associated viral vectors stimulates the hypothalamo‐pituitary‐gonadal axis. Biol Reprod[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2004;71:266. CrossRef

159. Keen‐RhinehartE, KalraSP, KalraPS. AAV‐mediated leptin receptor installation improves energy balance and the reproductive status of obese female koletsky rats. Peptides[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2005;26:2567. CrossRef

160. KonnerAC, JanoschekR, PlumL, et al.Insulin action in AgRP‐expressing neurons is required for suppression of hepatic glucose production. Cell Metab2007;5:438. CrossRef

161. RahmouniK, MorganDA. Hypothalamic arcuate nucleus mediates the sympathetic and arterial pressure responses to leptin. Hypertension[Research Support, Non‐U.S. Gov't]. 2007;49:647. CrossRef

162. FujikawaT, ChuangJC, SakataI, et al.Leptin therapy improves insulin‐deficient type 1 diabetes by CNS‐dependent mechanisms in mice. Proc Natl Acad Sci U S A[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;107:17391. CrossRef

163. YuX, ParkBH, WangMY, et al.Making insulin‐deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci U S A[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, Non‐P.H.S.]. 2008;105:14070. CrossRef

164. FujikawaT, BerglundED, PatelVR, et al.Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin. Cell Metab2013;18:431. CrossRef

165. WangMY, ChenL, ClarkGO, et al.Leptin therapy in insulin‐deficient type I diabetes. Proc Natl Acad Sci U S A[Research Support, Non‐U.S. Gov't]. 2010;107:4813. CrossRef

166. KowalskiTJ, LiuSM, LeibelRL, et al.Transgenic complementation of leptin‐receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR‐null mice expressing a LEPR‐B transgene. Diabetes[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2001;50:425. CrossRef

167. MortonGJ, SchwartzMW. Leptin and the central nervous system control of glucose metabolism. Physiol Rev[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2011;91:389. CrossRef

168. GermanJP, ThalerJP, WisseBE, et al.Leptin activates a novel CNS mechanism for insulin‐independent normalization of severe diabetic hyperglycemia. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2011;152:394. CrossRef

169. ObiciS, FengZ, TanJ, et al.Central melanocortin receptors regulate insulin action. J Clin Invest2001;108:1079. CrossRef

170. FanW, DinulescuDM, ButlerAA, et al.The central melanocortin system can directly regulate serum insulin levels. Endocrinology2000;141:3072.

171. HeijboerAC, van den HoekAM, PijlH, et al.Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice. Diabetologia[Research Support, Non‐U.S. Gov't]. 2005;48:1621. CrossRef

172. RossiJ, BalthasarN, OlsonD, et al.Melanocortin‐4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2011;13:195. CrossRef

173. TallamLS, da SilvaAA, HallJE. Melanocortin‐4 receptor mediates chronic cardiovascular and metabolic actions of leptin. Hypertension[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2006;48:58. CrossRef

174. SuttonGM, TrevaskisJL, HulverMW, et al.Diet‐genotype interactions in the development of the obese, insulin‐resistant phenotype of C57BL/6J mice lacking melanocortin‐3 or ‐4 receptors. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2006;147:2183. CrossRef

175. NogueirasR, WiedmerP, Perez‐TilveD, et al.The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest[Research Support, Non‐U.S. Gov't]. 2007;117:3475. CrossRef

176. Perez‐TilveD, HofmannSM, BasfordJ, et al.Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nat Neurosci[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;13:877. CrossRef

177. FarooqiIS, KeoghJM, YeoGS, et al.Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med2003;348:1085. CrossRef

178. FarooqiIS, YeoGS, KeoghJM, et al.Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest2000;106:271. CrossRef

179. HatoumIJ, StylopoulosN, VanhooseAM, et al.Melanocortin‐4 receptor signaling is required for weight loss after gastric bypass surgery. J Clin Endocrinol Metab[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2012;97:E1023. CrossRef

180. LoosRJ, LindgrenCM, LiS, et al.Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet2008;40:768. CrossRef

181. Gutierrez‐JuarezR, ObiciS, RossettiL. Melanocortin‐independent effects of leptin on hepatic glucose fluxes. J Biol Chem[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2004;279:49704. CrossRef

182. ShiH, SorrellJE, CleggDJ, et al.The roles of leptin receptors on POMC neurons in the regulation of sex‐specific energy homeostasis. Physiol Behav2010;100:165. CrossRef

183. CoppariR, IchinoseM, LeeCE, et al.The hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2005;1:63. CrossRef

184. GermanJ, KimF, SchwartzGJ, et al.Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2009;150:4502. CrossRef

185. LamCK, ChariM, SuBB, et al.Activation of N‐methyl‐D‐aspartate (NMDA) receptors in the dorsal vagal complex lowers glucose production. J Biol Chem[Research Support, Non‐U.S. Gov't]. 2010;285:21913. CrossRef

186. LamTK, PocaiA, Gutierrez‐JuarezR, et al.Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2005;11:320. CrossRef

187. CardinS, PagliassottiMJ, MooreMC, et al.Vagal cooling and concomitant portal norepinephrine infusion do not reduce net hepatic glucose uptake in conscious dogs. Am J Physiol Regul Integr Comp Physiol[Research Support, U.S. Gov't, P.H.S.]. 2004;287:R742. CrossRef

188. CardinS, WalmsleyK, NealDW, et al.Involvement of the vagus nerves in the regulation of basal hepatic glucose production in conscious dogs. Am J Physiol Endocrinol Metab[Research Support, U.S. Gov't, P.H.S.]. 2002;283:E958. CrossRef

189. GautronL, LeeC, FunahashiH, et al.Melanocortin‐4 receptor expression in a vago‐vagal circuitry involved in postprandial functions. J Comp Neurol[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;518:6. CrossRef

190. LiJH, GautamD, HanSJ, et al.Hepatic muscarinic acetylcholine receptors are not critically involved in maintaining glucose homeostasis in mice. Diabetes[Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non‐U.S. Gov't]. 2009;58:2776. CrossRef

191. BerthoudHR. The vagus nerve, food intake and obesity. Regul Pept2008;149:15. CrossRef

192. BerthoudHR, CarlsonNR, PowleyTL. Topography of efferent vagal innervation of the rat gastrointestinal tract. Am J Physiol1991;260(1 Pt 2):R200.

193. FriedmanMI, SawchenkoPE. Evidence for hepatic involvement in control of ad libitum food intake in rats. Am J Physiol[Research Support, U.S. Gov't, P.H.S.]. 1984;247(1 Pt 2):R106.

194. SawchenkoPE, FriedmanMI. Sensory functions of the liver–a review. Am J Physiol[Research Support, U.S. Gov't, P.H.S. Review]. 1979;236:R5.

195. EliasCF, LeeC, KellyJ, et al.Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron1998;21:1375. CrossRef

196. KishiT, AschkenasiCJ, LeeCE, et al.Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol2003;457:213. CrossRef

197. SohnJW, HarrisLE, BerglundED, et al.Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2013;152:612. CrossRef

198. BarshGS, SchwartzMW. Genetic approaches to studying energy balance: perception and integration. Nat Rev Genet2002;3:589.

199. FarooqiIS, O'RahillyS. Monogenic human obesity syndromes. Recent Prog Horm Res2004;59:409. CrossRef

200. GreenfieldJR, MillerJW, KeoghJM, et al.Modulation of blood pressure by central melanocortinergic pathways. N Engl J Med[Research Support, Non‐U.S. Gov't]. 2009;360:44. CrossRef

201. YeoGS, FarooqiIS, AminianS, et al.A frameshift mutation in MC4R associated with dominantly inherited human obesity [letter]. Nat Genet1998;20:111. CrossRef

202. YeoGS, LankEJ, FarooqiIS, et al.Mutations in the human melanocortin‐4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms. Hum Mol Genet2003;12:561. CrossRef

203. KrudeH, BiebermannH, LuckW, et al.Severe early‐onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet1998;19:155. CrossRef

204. VaisseC, ClementK, Guy‐GrandB, et al.A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet1998;20:113. CrossRef

205. WardMP, MosherJT, CrewsST. Regulation of bHLH‐PAS protein subcellular localization during Drosophila embryogenesis. Development1998;125:1599.

206. FanCM, KuwanaE, BulfoneA, et al.Expression patterns of two murine homologs of drosophila single‐minded suggest possible roles in embryonic patterning and in the pathogenesis of down syndrome. Mol Cell Neurosci1996;7:1. CrossRef

207. BalthasarN, DalgaardLT, LeeCE, et al.Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell2005;123:493. CrossRef

208. HolderJLJr, ButteNF, ZinnAR. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet2000;9:101. CrossRef

209. FarooqiIS, O'RahillyS. Monogenic obesity in humans. Annu Rev Med2005;56:443. CrossRef

210. MichaudJL, RosenquistT, MayNR, et al.Development of neuroendocrine lineages requires the bHLH‐PAS transcription factor SIM1. Genes Dev1998;12:3264. CrossRef

211. XuC, FanCM. Allocation of paraventricular and supraoptic neurons requires Sim1 function: a role for a Sim1 downstream gene PlexinC1. Mol Endocrinol2007;21:1234. CrossRef

212. HolderJLJr, ZhangL, KublaouiBM, et al.Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice. Am J Physiol Endocrinol Metab2004;287:E105. CrossRef

213. KublaouiBM, HolderJLJr, GemelliT, et al.Sim1 haploinsufficiency impairs melanocortin‐mediated anorexia and activation of paraventricular nucleus neurons. Mol Endocrinol2006;20:2483. CrossRef

214. BinghamNC, AndersonKK, ReuterAL, et al.Selective loss of leptin receptors in the ventromedial hypothalamic nucleus results in increased adiposity and a metabolic syndrome. Endocrinology2008;149:2138. CrossRef

215. DhillonH, ZigmanJM, YeC, et al.Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body‐weight homeostasis. Neuron2006;49:191. CrossRef

216. IkedaY, LuoX, AbbudR, et al.The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus. Mol Endocrinol1995;9:478.

217. MajdicG, YoungM, Gomez‐SanchezE, et al.Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology2002;143:607. CrossRef

218. KimKW, SohnJW, KohnoD, et al.SF‐1 in the ventral medial hypothalamic nucleus: a key regulator of homeostasis. Mol Cell Endocrinol[Research Support, N.I.H., Extramural Review]. 2011;336:219. CrossRef

219. KimKW, ZhaoL, DonatoJJr, et al.Steroidogenic factor 1 directs programs regulating diet‐induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus. Proc Natl Acad Sci U S A2011;●●:●●.

220. ElmquistJK, BjorbaekC, AhimaRS, et al.Distributions of leptin receptor mRNA isoforms in the rat brain. J Comp Neurol1998;395:535. CrossRef

221. MinokoshiY, HaqueMS, ShimazuT. Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes1999;48:287. CrossRef

222. ShiuchiT, HaqueMS, OkamotoS, et al.Hypothalamic orexin stimulates feeding‐associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab[Research Support, Non‐U.S. Gov't]. 2009;10:466. CrossRef

223. HaqueMS, MinokoshiY, HamaiM, et al.Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes[Research Support, Non‐U.S. Gov't]. 1999;48:1706. CrossRef

224. ZhangR, DhillonH, YinH, et al.Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology[Research Support, N.I.H., Extramural]. 2008;149:5654. CrossRef

225. FoxEA. A genetic approach for investigating vagal sensory roles in regulation of gastrointestinal function and food intake. Auton Neurosci[Comparative Study Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2006;126–127:9. CrossRef

226. BerthoudHR, NeuhuberWL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci2000;85:1. CrossRef

227. PrechtlJC, PowleyTL. The fiber composition of the abdominal vagus of the rat. Anat Embryol (Berl)1990;181:101. CrossRef

228. AltschulerSM, BaoXM, BiegerD, et al.Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts. J Comp Neurol1989;283:248. CrossRef

229. BerthoudHR, FoxEA, PowleyTL. Localization of vagal preganglionics that stimulate insulin and glucagon secretion. Am J Physiol1990;258(1 Pt 2):R160.

230. BerthoudHR, KresselM, NeuhuberWL. Vagal afferent innervation of rat abdominal paraganglia as revealed by anterograde DiI‐tracing and confocal microscopy. Acta Anat (Basel)1995;152:127. CrossRef

231. RinamanL, MiselisRR. The organization of vagal innervation of rat pancreas using cholera toxin‐horseradish peroxidase conjugate. J Auton Nerv Syst1987;21:109. CrossRef

232. WangFB, PowleyTL. Topographic inventories of vagal afferents in gastrointestinal muscle. J Comp Neurol2000;421:302. CrossRef

233. LiddleRA. Regulation of cholecystokinin secretion by intraluminal releasing factors. Am J Physiol[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, Non‐P.H.S. Research Support, U.S. Gov't, P.H.S. Review]. 1995;269(3 Pt 1):G319.

234. GibbsJ, FalascoJD, McHughPR. Cholecystokinin‐decreased food intake in rhesus monkeys. Am J Physiol1976;230:15.

235. GibbsJ, SmithGP. Cholecystokinin and satiety in rats and rhesus monkeys. Am J Clin Nutr1977;30:758.

236. MoranTH, AmeglioPJ, SchwartzGJ, et al.Blockade of type A, not type B, CCK receptors attenuates satiety actions of exogenous and endogenous CCK. Am J Physiol1992;262(1 Pt 2):R46.

237. BrobergerC, HolmbergK, ShiTJ, et al.Expression and regulation of cholecystokinin and cholecystokinin receptors in rat nodose and dorsal root ganglia. Brain Res[Research Support, Non‐U.S. Gov't]. 2001;903:128. CrossRef

238. PattersonLM, ZhengH, BerthoudHR. Vagal afferents innervating the gastrointestinal tract and CCKA‐receptor immunoreactivity. Anat Rec[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2002;266:10. CrossRef

239. BarrachinaMD, MartínezV, WangL, et al.Synergistic interaction between leptin and cholecystokinin to reduce short‐term food intake in lean mice. Proc Natl Acad Sci U S A1997;94:10455. CrossRef

240. EmondM, SchwartzGJ, LadenheimEE, et al.Central leptin modulates behavioral and neural responsivity to CCK. Am J Physiol1999;276(5 Pt 2):R1545.

241. SuttonGM, DuosB, PattersonLM, et al.Melanocortinergic modulation of cholecystokinin‐induced suppression of feeding through extracellular signal‐regulated kinase signaling in rat solitary nucleus. Endocrinology2005;146:3739. CrossRef

242. HuoL, MaengL, BjorbaekC, et al.Leptin and the control of food intake: neurons in the nucleus of the solitary tract are activated by both gastric distension and leptin. Endocrinology[Research Support, N.I.H., Extramural]. 2007;148:2189. CrossRef

243. GautronL, RutkowskiJM, BurtonMD, et al.Neuronal and nonneuronal cholinergic structures in the mouse gastrointestinal tract and spleen. J Comp Neurol2013;●●:●●.

244. GautronL, SakataI, UditS, et al.Genetic tracing of Nav1.8‐expressing vagal afferents in the mouse. J Comp Neurol[Research Support, N.I.H., Extramural]. 2011;519:3085. CrossRef

245. WilliamsDL, KaplanJM, GrillHJ. The role of the dorsal vagal complex and the vagus nerve in feeding effects of melanocortin‐3/4 receptor stimulation. Endocrinology2000;141:1332.

246. ConeRD, SimerlyRB. Leptin grows up and gets a neural network. Neuron[Comment].2011;71:4. CrossRef

247. HalfordJC, BoylandEJ, LawtonCL, et al.Serotonergic anti‐obesity agents: past experience and future prospects. Drugs[Review].2011;71:2247. CrossRef

248. HalfordJC, BoylandEJ, BlundellJE, et al.Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol[Review].2010;6:255. CrossRef

249. HalfordJC, HarroldJA, BoylandEJ, et al.Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs[Research Support, Non‐U.S. Gov't Review]. 2007;67:27. CrossRef

250. BlundellJE, HalfordJC. Pharmacological aspects of obesity treatment: towards the 21st century. Int J Obes Relat Metab Disord[Review].1995;19(Suppl 3):S51.

251. RowlandNE, RokadiaS, GreenDJ, et al.Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d‐norfenfluramine or d‐fenfluramine. Pharmacol Biochem Behav[Comparative Study]. 2004;77:541. CrossRef

252. RowlandNE, CarltonJ. Neurobiology of an anorectic drug: fenfluramine. Prog Neurobiol[Review].1986;27:13. CrossRef

253. McGuirkJ, MuscatR, WillnerP. Effects of chronically administered fluoxetine and fenfluramine on food intake, body weight and the behavioural satiety sequence. Psychopharmacology (Berl)1992;106:401. CrossRef

254. GoodallE, FeeneyS, McGuirkJ, et al.A comparison of the effects of d‐ and l‐fenfluramine and d‐amphetamine on energy and macronutrient intake in human subjects. Psychopharmacology (Berl)[Clinical Trial Comparative Study Controlled Clinical Trial Randomized Controlled Trial Research Support, Non‐U.S. Gov't]. 1992;106:221. CrossRef

255. McGuirkJ, GoodallE, SilverstoneT, et al.Differential effects of d‐fenfluramine, l‐fenfluramine and d‐amphetamine on the microstructure of human eating behaviour. Behav Pharmacol1991;2:113. CrossRef

256. WillnerP, McGuirkJ, PhillipsG, et al.Behavioural analysis of the anorectic effects of fluoxetine and fenfluramine. Psychopharmacology (Berl)1990;102:273. CrossRef

257. SouquetAM, RowlandNE. Effect of chronic administration of dexfenfluramine on stress‐ and palatability‐induced food intake in rats. Physiol Behav[Research Support, Non‐U.S. Gov't]. 1989;46:145. CrossRef

258. BlundellJE, LawtonCL, HalfordJC. Serotonin, eating behavior, and fat intake. Obes Res[Research Support, Non‐U.S. Gov't Review]. 1995;3(Suppl 4):471S. CrossRef

259. BlundellJE, LeshemMB. Central action of anorexic agents: effects of amphetamine and fenfluramine in rats with lateral hypothalamic lesions. Eur J Pharmacol[Comparative Study]. 1974;28:81. CrossRef

260. GeyerMA, PuertoA, MenkesDB, et al.Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. Brain Res[Research Support, U.S. Gov't, Non‐P.H.S. Research Support, U.S. Gov't, P.H.S.]. 1976;106:257. CrossRef

261. GeyerMA, PuertoA, DawseyWJ, et al.Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways. Brain Res[Research Support, U.S. Gov't, P.H.S.]. 1976;106:241. CrossRef

262. ConnollyHM, CraryJL, McGoonMD, et al.Valvular heart disease associated with fenfluramine‐phentermine. N Engl J Med[Case Reports]. 1997;337:581. CrossRef

263. BelloNT, LiangNC. The use of serotonergic drugs to treat obesity–is there any hope?Drug Des Devel Ther[Review].2011;5:95. CrossRef

264. GarfieldAS, HeislerLK. Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2009;587(Pt 1):49. CrossRef

265. NonogakiK, StrackAM, DallmanMF, et al.Leptin‐independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5‐HT2C receptor gene. Nat Med1998;4:1152. CrossRef

266. TecottLH, SunLM, AkanaSF, et al.Eating disorder and epilepsy in mice lacking 5‐HT2c serotonin receptors. Nature1995;374:542. CrossRef

267. VickersSP, CliftonPG, DourishCT, et al.Reduced satiating effect of d‐fenfluramine in serotonin 5‐HT(2C) receptor mutant mice. Psychopharmacology (Berl)1999;143:309. CrossRef

268. HeislerLK, CowleyMA, KishiT, et al.Central serotonin and melanocortin pathways regulating energy homeostasis. Ann N Y Acad Sci2003;994:169. CrossRef

269. HeislerLK, CowleyMA, TecottLH, et al.Activation of central melanocortin pathways by fenfluramine. Science[Research Support, Non‐U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. 2002;297:609. CrossRef

270. HeislerLK, JobstEE, LeeCE, et al.Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron2006;●●:●●. In Press.

271. XuY, JonesJE, KohnoD, et al.5‐HT2CRs expressed by pro‐opiomelanocortin neurons regulate energy homeostasis. Neuron2008;60:582. CrossRef

272. ZhouL, SuttonGM, RochfordJJ, et al.Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin‐4 receptor signaling pathways. Cell Metab2007;6:398. CrossRef

273. ColmanE, GoldenJ, RobertsM, et al.The FDA's assessment of two drugs for chronic weight management. N Engl J Med2012;367:1577. CrossRef

274. TeffKL, KimSF. Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism. Physiol Behav[Research Support, N.I.H., Extramural Review]. 2011;104:590. CrossRef

275. TemplemanLA, ReynoldsGP, ArranzB, et al.Polymorphisms of the 5‐HT2C receptor and leptin genes are associated with antipsychotic drug‐induced weight gain in Caucasian subjects with a first‐episode psychosis. Pharmacogenet Genomics[Research Support, Non‐U.S. Gov't]. 2005;15:195. CrossRef

276. ReynoldsGP, TemplemanLA, ZhangZJ. The role of 5‐HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry[Research Support, Non‐U.S. Gov't Review]. 2005;29:1021. CrossRef

277. KishoreS, StammS. Regulation of alternative splicing by snoRNAs. Cold Spring Harb Symp Quant Biol[Research Support, Non‐U.S. Gov't Review]. 2006;71:329. CrossRef

278. KishoreS, StammS. The snoRNA HBII‐52 regulates alternative splicing of the serotonin receptor 2C. Science[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2006;311:230. CrossRef

279. WadeJM, JunejaP, MacKayAW, et al.Synergistic impairment of glucose homeostasis in ob/ob mice lacking functional serotonin 2C receptors. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2008;149:955. CrossRef

280. XuY, BerglundED, SohnJW, et al.5‐HT2CRs expressed by pro‐opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci[Comparative Study Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2010;13:1457. CrossRef

281. MarstonOJ, GarfieldAS, HeislerLK. Role of central serotonin and melanocortin systems in the control of energy balance. Eur J Pharmacol[Research Support, Non‐U.S. Gov't Review]. 2011;660:70. CrossRef

282. LamDD, HeislerLK. Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes. Expert Rev Mol Med[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't Review]. 2007;9:1.

283. SmithSR, WeissmanNJ, AndersonCM, et al.Multicenter, placebo‐controlled trial of lorcaserin for weight management. N Engl J Med[Multicenter Study Randomized Controlled Trial Research Support, Non‐U.S. Gov't]. 2010;363:245. CrossRef

284. LamDD, PrzydzialMJ, RidleySH, et al.Serotonin 5‐HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2008;149:1323. CrossRef

285. ZhouL, SuttonGM, RochfordJJ, et al.Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin‐4 receptor signaling pathways. Cell Metab[Research Support, N.I.H., Extramural Research Support, Non‐U.S. Gov't]. 2007;6:398. CrossRef

286. UngerRH, SchererPE. Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocrinol Metab[Review].2010;21:345. CrossRef

287. ElmquistJK, MarcusJN. Rethinking the central causes of diabetes. Nat Med2003;9:645. CrossRef

288. ConsidineRV, SinhaMK, HeimanML, et al.Serum immunoreactive‐leptin concentrations in normal‐weight and obese humans. N Engl J Med1996;334:292. CrossRef