The Role of PVH Circuits in Leptin Action and Energy Balance

Annual Review of Physiology

Volumn 78, Issue , 2016, Pages 207-221

  Sutton, Amy K ^a   Myers, Martin G ^a   Olson, David P ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Brain stem; Feeding; Hypothalamus; Leptin; Melanocortins; Neuropeptides; NOS1; Obesity; PVH

Indexed keywords

4 AMINOBUTYRIC ACID; GHRELIN; INSULIN; LEPTIN; MELANOCORTIN; NEURONAL NITRIC OXIDE SYNTHASE; NEUROPEPTIDE Y; VESICULAR INHIBITORY AMINO ACID TRANSPORTER;

ARCUATE NUCLEUS; BASAL METABOLIC RATE; BODY WEIGHT; BRAIN FUNCTION; BRAIN REGION; BRAIN STEM; CALORIC RESTRICTION; ENERGY BALANCE; ENERGY EXPENDITURE; FEEDING BEHAVIOR; FOOD INTAKE; HORMONE ACTION; HUMAN; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; HYPOTHALAMUS; NONHUMAN; OBESITY; PARABRACHIAL NUCLEUS; PREOPTIC AREA; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STRESS; ANIMAL; EATING; ENERGY METABOLISM; METABOLISM; NERVE CELL; PHYSIOLOGY;

ANIMALS; ARCUATE NUCLEUS OF HYPOTHALAMUS; EATING; ENERGY METABOLISM; HUMANS; LEPTIN; NEURONS; PARAVENTRICULAR HYPOTHALAMIC NUCLEUS;

EID: 84958675054     PISSN: 00664278     EISSN: 15451585     Source Type: Book Series    
DOI: 10.1146/annurev-physiol-021115-105347     Document Type: Review

References (99)

1. Finkelstein EA, Trogdon JG, Cohen JW, DietzW. 2009. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff. 28(5):W822-31
2. O'Rahilly S, Farooqi IS. 2000. The genetics of obesity in humans. Endocr. Rev. 27(7):710-18
3. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, et al. 2015. Genetic studies of body mass index yield new insights for obesity biology. Nature 518(7538):197-206
4. Schwartz MW,Woods SC, Porte D, Seeley RJ, Baskin DG. 2000. Central nervous system control of food intake. Nature 404(6778):661-71
5. Myers MG, Leibel RL. 2000. Lessons from rodent models of obesity. In Endotext, ed. LJ De Groot, P Beck-Peccoz, G Chrousos, K Dungan, A Grossman, et al. South Dartmouth, MA: MDText.com
6. Ingalls AM,DickieMM,Snell GD. 1950. Obese, a new mutation in the housemouse. J. Hered. 41(12):317-18
7. Hummel KP, Dickie MM, Coleman DL. 1966. Diabetes, a new mutation in the mouse. Science 153(3740):1127-28
8. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, et al. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269(5223):543-46
9. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, et al. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269(5223):540-43
10. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. 1995. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269(5223):546-49
11. RosenbaumM,Goldsmith R, Bloomfield D, Magnano A,Weimer L, et al. 2005. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J. Clin. Investig. 115(12):3579-86
12. Ahima RS, Prabakaran D, Mantzoros C,QuD, Lowell B, et al. 1996. Role of leptin in the neuroendocrine response to fasting. Nature 382(6588):250-52
13. Kloek C, Haq AK, Dunn SL, Lavery HJ, Banks AS, Myers MG. 2002. Regulation of Jak kinases by intracellular leptin receptor sequences. J. Biol. Chem. 277(44):41547-55
14. Patterson CM, Leshan RL, Jones JC, Myers MG. 2011. Molecular mapping of mouse brain regions innervated by leptin receptor-expressing cells. Brain Res. 1378:18-28
15. Elmquist JK, Bjørbaek C, Ahima RS, Flier JS, Saper CB. 1998. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395(4):535-47
16. Scott MM, Lachey JL, Sternson SM, Lee CE, Elias CF, et al. 2009. Leptin targets in the mouse brain. J. Comp. Neurol. 514(5):518-32
17. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, et al. 1997. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387(6636):903-8
18. Barsh GS, He L, Gunn TM. 2002. Genetic and biochemical studies of the Agouti-attractin system. J. Recept. Signal Transduct. Res. 22(1-4):63-77
19. Lu D, Willard D, Patel IR, Kadwell S, Overton L, et al. 1994. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371(6500):799-802
20. Marsh DJ, Hollopeter G, Huszar D, Laufer R, Yagaloff KA, et al. 1999. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21(1):119-22
21. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, et al. 1997. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88(1):131-41
22. Butler AA, Kesterson RA, Khong K, Cullen MJ, Pelleymounter MA, et al. 2000. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141(9):3518-21
23. Chen AS, Marsh DJ, Trumbauer ME, Frazier EG, Guan XM, et al. 2000. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26(1):97-102
24. Vaisse C, Clement K, Guy-Grand B, Froguel P. 1998. A frameshiftmutation in humanMC4Ris associated with a dominant form of obesity. Nat. Genet. 20(2):113-14
25. Loos RJF, Lindgren CM, Li S, Wheeler E, Zhao JH, et al. 2008. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40(6):768-75
26. Hetherington AW, Ranson SW. 1940. Hypothalamic lesions and adiposity in the rat. Nutr. Rev. 41:4
27. Stevenson JA. 1969. VI. Sensory mechanisms and multi-factor models in the regulation of food and water intake. Mechanisms in the control of food and water intake. Ann. N. Y. Acad. Sci. 157(2):1069-83
28. Choi S, Sparks R, Clay M, Dallman MF. 1999. Rats with hypothalamic obesity are insensitive to central leptin injections. Endocrinology 140(10):4426-33
29. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, et al. 1997. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278(5335):135-38
30. Yeo GSH, Heisler LK. 2012. Unraveling the brain regulation of appetite: lessons from genetics. Nat. Neurosci. 15(10):1343-49
31. Cheung CC, Clifton DK, Steiner RA. 1997. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138(10):4489-92
32. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, et al. 2001. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411(6836):480-84
33. Thornton JE, Cheung CC, Clifton DK, Steiner RA. 1997. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138(11):5063-66
34. Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD. 1999. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 24(1):155-63
35. Tong Q, Ye C-P, Jones JE, Elmquist JK, Lowell BB. 2008. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat. Neurosci. 11(9):998-1000
36. Hagan MM, Rushing PA, Pritchard LM, Schwartz MW, Strack AM, et al. 2000. Long-term orexigenic effects of AgRP-(83-132) involve mechanisms other than melanocortin receptor blockade. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279(1):R47-52
37. Rossi M, Kim MS, Morgan DG, Small CJ, Edwards CM, et al. 1998. A C-terminal fragment of Agoutirelated protein increases feeding and antagonizes the effect of α-melanocyte stimulating hormone in vivo. Endocrinology 139(10):4428-31
38. Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS, et al. 1999. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23(4):775-86
39. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, et al. 2004. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42(6):983-91
40. van deWall E, Leshan R, Xu AW, BalthasarN, Coppari R, et al. 2008. Collective and individual functions of leptin receptor modulated neurons controllingmetabolism and ingestion. Endocrinology 149(4):1773-85
41. Leshan RL,Greenwald-Yarnell M, Patterson CM,Gonzalez IE, MyersMG. 2012. Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance. Nat.Med. 18(5):820-23
42. Vong L, Ye C, Yang Z, Choi B, Chua S, Lowell BB. 2011. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71(1):142-54
43. Cowley MA, Smith RG, Diano S, Tsch öp M, Pronchuk N, et al. 2003. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37(4):649-61
44. Heisler LK, Cowley MA, Tecott LH, Fan W, Low MJ, et al. 2002. Activation of central melanocortin pathways by fenfluramine. Science 297(5581):609-11
45. Heisler LK, Jobst EE, Sutton GM, Zhou L, Borok E, et al. 2006. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51(2):239-49
46. Zheng H, Patterson LM, Rhodes CJ, Louis GW, Skibicka KP, et al. 2010. A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298(3):R720-28
47. Broberger C, Johansen J, Johansson C, Schalling M, Hökfelt T. 1998. The neuropeptide Y/agouti generelated protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. PNAS 95(25):15043-48
48. Wang D, He X, Zhao Z, Feng Q, Lin R, et al. 2015. Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons. Front. Neuroanat. 9:40
49. Bouret SG, Draper SJ, Simerly RB. 2004. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J. Neurosci. 24(11):2797-805
50. Gold RM. 1973. Hypothalamic obesity: the myth of the ventromedial nucleus. Science 182(4111):488-90
51. Sims JS, Lorden JF. 1986. Effect of paraventricular nucleus lesions on body weight, food intake and insulin levels. Behav. Brain Res. 22(3):265-81
52. Kishi T, AschkenasiCJ, LeeCE, Mountjoy KG, Saper CB,Elmquist JK. 2003. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J. Comp. Neurol. 457(3):213-35
53. Sawchenko PE, Swanson LW. 1982. The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res. 257(3):275-325
54. FulwilerCE, SaperCB. 1985. Cholecystokinin-immunoreactive innervation of the ventromedial hypothalamus in the rat: possible substrate for autonomic regulation of feeding. Neurosci. Lett. 53(3):289-96
55. Blevins JE, Schwartz MW, Baskin DG. 2004. Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287(1):R87-96
56. BalthasarN, Dalgaard LT, Lee CE, Yu J, FunahashiH, et al. 2005. Divergence ofmelanocortin pathways in the control of food intake and energy expenditure. Cell 123(3):493-505
57. Wu Q, BoyleMP, Palmiter RD. 2009. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell 137(7):1225-34
58. Carter ME, Soden ME, Zweifel LS, Palmiter RD. 2013. Genetic identification of a neural circuit that suppresses appetite. Nature 503(7474):111-14
59. Atasoy D, Betley JN, Su HH, Sternson SM. 2012. Deconstruction of a neural circuit for hunger. Nature 488(7410):172-77
60. Sutton AK, Pei H, Burnett KH, Myers MG. 2014. Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus. J. Neurosci. 34(46):15306-18
61. Garfield AS, Li C, Madara JC, Shah BP, Webber E, et al. 2015. A neural basis for melanocortin-4 receptor-regulated appetite. Nat. Neurosci. 18(6):863-71
62. Grill HJ, Hayes MR. 2012. Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance. Cell Metab. 16(3):296-309
63. Berthoud HR, Blackshaw LA, Brookes SJH, Grundy D. 2004. Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract. Neurogastroenterol. Motil. 16(Suppl. 1):28-33
64. Norgren R. 1978. Projections from the nucleus of the solitary tract in the rat. Neuroscience 3(2):207-18
65. Herbert H,Moga MM, Saper CB. 1990. Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J. Comp. Neurol. 293(4):540-80
66. Becskei C,Grabler V, Edwards GL, Riediger T, Lutz TA. 2007. Lesion of the lateral parabrachial nucleus attenuates the anorectic effect of peripheral amylin and CCK. Brain Res. 1162:76-84
67. Wu Q, Clark MS, Palmiter RD. 2012. Deciphering a neuronal circuit that mediates appetite. Nature 483(7391):594-97
68. D'Hanis W, Linke R, Yilmazer-Hanke DM. 2007. Topography of thalamic and parabrachial calcitonin gene-related peptide (CGRP) immunoreactive neurons projecting to subnuclei of the amygdala and extended amygdala. J. Comp. Neurol. 505(3):268-91
69. Schwaber JS, Sternini C, Brecha NC, Rogers WT, Card JP. 1988. Neurons containing calcitonin generelated peptide in the parabrachial nucleus project to the central nucleus of the amygdala. J. Comp. Neurol. 270(3):416-26
70. Shor-Posner G, Azar AP, Insinga S, Leibowitz SF. 1985. Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions. Physiol. Behav. 35(6):883-90
71. Michaud JL, Rosenquist T, May NR, Fan CM. 1998. Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Genes Dev. 12(20):3264-75
72. Holder JL, Butte NF, Zinn AR. 2000. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum. Mol. Genet. 9(1):101-8
73. Shah BP, Vong L, Olson DP, Koda S, Krashes MJ, et al. 2014. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. PNAS 111(36):13193-98
74. Rossi J, Balthasar N, Olson D, Scott M, Berglund E, et al. 2011. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 13(2):195-204
75. Xu Y, Wu Z, Sun H, Zhu Y, Kim ER, et al. 2013. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab. 18(6):860-70
76. Blevins JE, Eakin TJ, Murphy JA, Schwartz MW, Baskin DG. 2003. Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin. Brain Res. 993(1-2):30-41
77. Kublaoui BM, Gemelli T, Tolson KP,Wang Y,Zinn AR. 2008. Oxytocin deficiencymediates hyperphagic obesity of Sim1 haploinsufficient mice. Mol. Endocrinol. 22(7):1723-34
78. Takayanagi Y, Kasahara Y, Onaka T, Takahashi N, Kawada T, Nishimori K. 2008. Oxytocin receptor-deficient mice developed late-onset obesity. NeuroReport 19(9):951-55
79. Camerino C. 2009. Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity 17(5):980-84
80. Wu Z, Xu Y, Zhu Y, Sutton AK, Zhao R, et al. 2012. An obligate role of oxytocin neurons in diet induced energy expenditure. PLOS ONE 7(9):e45167
81. Biag J, Huang Y, Gou L, Hintiryan H, Askarinam A, et al. 2012. Cyto-and chemoarchitecture of the hypothalamic paraventricular nucleus in the C57BL/6J male mouse: a study of immunostaining and multiple fluorescent tract tracing. J. Comp. Neurol. 520(1):6-33
82. Sawchenko PE, Swanson LW. 1983. The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog. Brain Res. 60:19-29
83. Ziegler DR, Edwards MR, Ulrich-Lai YM, Herman JP, Cullinan WE. 2012. Brainstem origins of glutamatergic innervation of the rat hypothalamic paraventricular nucleus. J. Comp. Neurol. 520(11):2369-94
84. Ulrich-Lai YM, Jones KR, Ziegler DR, Cullinan WE,Herman JP. 2011. Forebrain origins of glutamatergic innervation to the rat paraventricular nucleus of the hypothalamus: differential inputs to the anterior versus posterior subregions. J. Comp. Neurol. 519(7):1301-19
85. Herman JP, Tasker JG, Ziegler DR, Cullinan WE. 2002. Local circuit regulation of paraventricular nucleus stress integration: glutamate-GABA connections. Pharmacol. Biochem. Behav. 71(3):457-68
86. Boudaba C, Schrader LA, Tasker JG. 1997. Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus. J. Neurophysiol. 77(6):3396-400
87. Ziegler DR, Herman JP. 2000. Local integration of glutamate signaling in the hypothalamic paraventricular region: regulation of glucocorticoid stress responses. Endocrinology 141(12):4801-4
88. Krashes MJ, Shah BP, Madara JC, Olson DP, Strochlic DE, et al. 2014. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature 507(7491):238-42
89. Xi D, Gandhi N, LaiM,KublaouiBM.2012. Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. PLOS ONE 7(4):e36453
90. Tolson KP, Gemelli T, Meyer D, Yazdani U, Kozlitina J, Zinn AR. 2014. Inducible neuronal inactivation of Sim1 in adult mice causes hyperphagic obesity. Endocrinology 155(7):2436-44
91. Madden CJ, Morrison SF. 2009. Neurons in the paraventricular nucleus of the hypothalamus inhibit sympathetic outflow to brown adipose tissue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296(3):R831-43
92. Bamshad M, Song CK, Bartness TJ. 1999. CNS origins of the sympathetic nervous system outflow to brown adipose tissue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 276(6, Part 2):R1569-78
93. Caverson MM, Ciriello J, Calaresu FR. 1984. Paraventricular nucleus of the hypothalamus: an electrophysiological investigation of neurons projecting directly to intermediolateral nucleus in the cat. Brain Res. 305(2):380-83
94. Cao W-H, Madden CJ, Morrison SF. 2010. Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299(1):R277-90
95. Morrison SF, Madden CJ, Tupone D. 2014. Central neural regulation of brown adipose tissue thermogenesis and energy expenditure. Cell Metab. 19(5):741-56
96. Kong D, Tong Q, Ye C, Koda S, Fuller PM, et al. 2012. GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure. Cell 151(3):645-57
97. Dodd GT,Decherf S, LohK, Simonds SE,Wiede F, et al. 2015. Leptin and insulin act onPOMCneurons to promote the browning of white fat. Cell 160(1-2):88-104
98. Enriori PJ, Sinnayah P, Simonds SE,Garcia RudazC,CowleyMA. 2011. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J. Neurosci. 31(34):12189-97
99. Lindberg D, Chen P, Li C. 2013. Conditional viral tracing reveals that steroidogenic factor 1-positive neurons of the dorsomedial subdivision of the ventromedial hypothalamus project to autonomic centers of the hypothalamus and hindbrain. J. Comp. Neurol. 521(14):3167-90