1932

Abstract

Although it has been known for more than a century that the brain controls overall energy balance and adiposity by regulating feeding behavior and energy expenditure, the roles for individual brain regions and neuronal subtypes were not fully understood until recently. This area of research is active, and as such our understanding of the central regulation of energy balance is continually being refined as new details emerge. Much of what we now know stems from the discoveries of leptin and the hypothalamic melanocortin system. Hypothalamic circuits play a crucial role in the control of feeding and energy expenditure, and within the hypothalamus, the arcuate nucleus (ARC) functions as a gateway for hormonal signals of energy balance, such as leptin. It is also well established that the ARC is a primary residence for hypothalamic melanocortinergic neurons. The paraventricular hypothalamic nucleus (PVH) receives direct melanocortin input, along with other integrated signals that affect energy balance, and mediates the majority of hypothalamic output to control both feeding and energy expenditure. Herein, we review in detail the structure and function of the ARC-PVH circuit in mediating leptin signaling and in regulating energy balance.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021115-105347
2016-02-10
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/physiol/78/1/annurev-physiol-021115-105347.html?itemId=/content/journals/10.1146/annurev-physiol-021115-105347&mimeType=html&fmt=ahah

Literature Cited

  1. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. 1.  2009. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff. 28:5W822–31 [Google Scholar]
  2. O'Rahilly S, Farooqi IS. 2.  2000. The genetics of obesity in humans. Endocr. Rev. 27:7710–18 [Google Scholar]
  3. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH. 3.  et al. 2015. Genetic studies of body mass index yield new insights for obesity biology. Nature 518:7538197–206 [Google Scholar]
  4. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. 4.  2000. Central nervous system control of food intake. Nature 404:6778661–71 [Google Scholar]
  5. Myers MG, Leibel RL. 5.  2000. Lessons from rodent models of obesity. Endotext LJ De Groot, P Beck-Peccoz, G Chrousos, K Dungan, A Grossman, et al. South Dartmouth, MA: MDText.com
  6. Ingalls AM, Dickie MM, Snell GD. 6.  1950. Obese, a new mutation in the house mouse. J. Hered. 41:12317–18 [Google Scholar]
  7. Hummel KP, Dickie MM, Coleman DL. 7.  1966. Diabetes, a new mutation in the mouse. Science 153:37401127–28 [Google Scholar]
  8. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT. 8.  et al. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:5223543–46 [Google Scholar]
  9. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D. 9.  et al. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:5223540–43 [Google Scholar]
  10. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. 10.  1995. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269:5223546–49 [Google Scholar]
  11. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L. 11.  et al. 2005. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J. Clin. Investig. 115:123579–86 [Google Scholar]
  12. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B. 12.  et al. 1996. Role of leptin in the neuroendocrine response to fasting. Nature 382:6588250–52 [Google Scholar]
  13. Kloek C, Haq AK, Dunn SL, Lavery HJ, Banks AS, Myers MG. 13.  2002. Regulation of Jak kinases by intracellular leptin receptor sequences. J. Biol. Chem. 277:4441547–55 [Google Scholar]
  14. Patterson CM, Leshan RL, Jones JC, Myers MG. 14.  2011. Molecular mapping of mouse brain regions innervated by leptin receptor–expressing cells. Brain Res. 1378:18–28 [Google Scholar]
  15. Elmquist JK, Bjørbaek C, Ahima RS, Flier JS, Saper CB. 15.  1998. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395:4535–47 [Google Scholar]
  16. Scott MM, Lachey JL, Sternson SM, Lee CE, Elias CF. 16.  et al. 2009. Leptin targets in the mouse brain. J. Comp. Neurol. 514:5518–32 [Google Scholar]
  17. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H. 17.  et al. 1997. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:6636903–8 [Google Scholar]
  18. Barsh GS, He L, Gunn TM. 18.  2002. Genetic and biochemical studies of the Agouti-attractin system. J. Recept. Signal Transduct. Res. 22:1–463–77 [Google Scholar]
  19. Lu D, Willard D, Patel IR, Kadwell S, Overton L. 19.  et al. 1994. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371:6500799–802 [Google Scholar]
  20. Marsh DJ, Hollopeter G, Huszar D, Laufer R, Yagaloff KA. 20.  et al. 1999. Response of melanocortin-4 receptor–deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21:1119–22 [Google Scholar]
  21. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q. 21.  et al. 1997. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:1131–41 [Google Scholar]
  22. Butler AA, Kesterson RA, Khong K, Cullen MJ, Pelleymounter MA. 22.  et al. 2000. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor–deficient mouse. Endocrinology 141:93518–21 [Google Scholar]
  23. Chen AS, Marsh DJ, Trumbauer ME, Frazier EG, Guan XM. 23.  et al. 2000. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26:197–102 [Google Scholar]
  24. Vaisse C, Clement K, Guy-Grand B, Froguel P. 24.  1998. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20:2113–14 [Google Scholar]
  25. Loos RJF, Lindgren CM, Li S, Wheeler E, Zhao JH. 25.  et al. 2008. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40:6768–75 [Google Scholar]
  26. Hetherington AW, Ranson SW. 26.  1940. Hypothalamic lesions and adiposity in the rat. Nutr. Rev. 41:4 [Google Scholar]
  27. Stevenson JA. 27.  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. 157:21069–83 [Google Scholar]
  28. Choi S, Sparks R, Clay M, Dallman MF. 28.  1999. Rats with hypothalamic obesity are insensitive to central leptin injections. Endocrinology 140:104426–33 [Google Scholar]
  29. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y. 29.  et al. 1997. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:5335135–38 [Google Scholar]
  30. Yeo GSH, Heisler LK. 30.  2012. Unraveling the brain regulation of appetite: lessons from genetics. Nat. Neurosci. 15:101343–49 [Google Scholar]
  31. Cheung CC, Clifton DK, Steiner RA. 31.  1997. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138:104489–92 [Google Scholar]
  32. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S. 32.  et al. 2001. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:6836480–84 [Google Scholar]
  33. Thornton JE, Cheung CC, Clifton DK, Steiner RA. 33.  1997. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138:115063–66 [Google Scholar]
  34. Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD. 34.  1999. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 24:1155–63 [Google Scholar]
  35. Tong Q, Ye C-P, Jones JE, Elmquist JK, Lowell BB. 35.  2008. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat. Neurosci. 11:9998–1000 [Google Scholar]
  36. Hagan MM, Rushing PA, Pritchard LM, Schwartz MW, Strack AM. 36.  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. 279:1R47–52 [Google Scholar]
  37. Rossi M, Kim MS, Morgan DG, Small CJ, Edwards CM. 37.  et al. 1998. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of α-melanocyte stimulating hormone in vivo. Endocrinology 139:104428–31 [Google Scholar]
  38. Elias CF, Aschkenasi C, Lee C, Kelly J, Ahima RS. 38.  et al. 1999. Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23:4775–86 [Google Scholar]
  39. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE. 39.  et al. 2004. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:6983–91 [Google Scholar]
  40. van de Wall E, Leshan R, Xu AW, Balthasar N, Coppari R. 40.  et al. 2008. Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology 149:41773–85 [Google Scholar]
  41. Leshan RL, Greenwald-Yarnell M, Patterson CM, Gonzalez IE, Myers MG. 41.  2012. Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance. Nat. Med. 18:5820–23 [Google Scholar]
  42. Vong L, Ye C, Yang Z, Choi B, Chua S, Lowell BB. 42.  2011. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71:1142–54 [Google Scholar]
  43. Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N. 43.  et al. 2003. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37:4649–61 [Google Scholar]
  44. Heisler LK, Cowley MA, Tecott LH, Fan W, Low MJ. 44.  et al. 2002. Activation of central melanocortin pathways by fenfluramine. Science 297:5581609–11 [Google Scholar]
  45. Heisler LK, Jobst EE, Sutton GM, Zhou L, Borok E. 45.  et al. 2006. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51:2239–49 [Google Scholar]
  46. Zheng H, Patterson LM, Rhodes CJ, Louis GW, Skibicka KP. 46.  et al. 2010. A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298:3R720–28 [Google Scholar]
  47. Broberger C, Johansen J, Johansson C, Schalling M, Hökfelt T. 47.  1998. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. PNAS 95:2515043–48 [Google Scholar]
  48. Wang D, He X, Zhao Z, Feng Q, Lin R. 48.  et al. 2015. Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons. Front. Neuroanat. 9:40 [Google Scholar]
  49. Bouret SG, Draper SJ, Simerly RB. 49.  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. 24:112797–805 [Google Scholar]
  50. Gold RM. 50.  1973. Hypothalamic obesity: the myth of the ventromedial nucleus. Science 182:4111488–90 [Google Scholar]
  51. Sims JS, Lorden JF. 51.  1986. Effect of paraventricular nucleus lesions on body weight, food intake and insulin levels. Behav. Brain Res. 22:3265–81 [Google Scholar]
  52. Kishi T, Aschkenasi CJ, Lee CE, Mountjoy KG, Saper CB, Elmquist JK. 52.  2003. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J. Comp. Neurol. 457:3213–35 [Google Scholar]
  53. Sawchenko PE, Swanson LW. 53.  1982. The organization of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat. Brain Res. 257:3275–325 [Google Scholar]
  54. Fulwiler CE, Saper CB. 54.  1985. Cholecystokinin-immunoreactive innervation of the ventromedial hypothalamus in the rat: possible substrate for autonomic regulation of feeding. Neurosci. Lett. 53:3289–96 [Google Scholar]
  55. Blevins JE, Schwartz MW, Baskin DG. 55.  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. 287:1R87–96 [Google Scholar]
  56. Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H. 56.  et al. 2005. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123:3493–505 [Google Scholar]
  57. Wu Q, Boyle MP, Palmiter RD. 57.  2009. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell 137:71225–34 [Google Scholar]
  58. Carter ME, Soden ME, Zweifel LS, Palmiter RD. 58.  2013. Genetic identification of a neural circuit that suppresses appetite. Nature 503:7474111–14 [Google Scholar]
  59. Atasoy D, Betley JN, Su HH, Sternson SM. 59.  2012. Deconstruction of a neural circuit for hunger. Nature 488:7410172–77 [Google Scholar]
  60. Sutton AK, Pei H, Burnett KH, Myers MG. 60.  2014. Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus. J. Neurosci. 34:4615306–18 [Google Scholar]
  61. Garfield AS, Li C, Madara JC, Shah BP, Webber E. 61.  et al. 2015. A neural basis for melanocortin-4 receptor–regulated appetite. Nat. Neurosci. 18:6863–71 [Google Scholar]
  62. Grill HJ, Hayes MR. 62.  2012. Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance. Cell Metab. 16:3296–309 [Google Scholar]
  63. Berthoud HR, Blackshaw LA, Brookes SJH, Grundy D. 63.  2004. Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract. Neurogastroenterol. Motil. 16:Suppl. 128–33 [Google Scholar]
  64. Norgren R. 64.  1978. Projections from the nucleus of the solitary tract in the rat. Neuroscience 3:2207–18 [Google Scholar]
  65. Herbert H, Moga MM, Saper CB. 65.  1990. Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J. Comp. Neurol. 293:4540–80 [Google Scholar]
  66. Becskei C, Grabler V, Edwards GL, Riediger T, Lutz TA. 66.  2007. Lesion of the lateral parabrachial nucleus attenuates the anorectic effect of peripheral amylin and CCK. Brain Res. 1162:76–84 [Google Scholar]
  67. Wu Q, Clark MS, Palmiter RD. 67.  2012. Deciphering a neuronal circuit that mediates appetite. Nature 483:7391594–97 [Google Scholar]
  68. D'Hanis W, Linke R, Yilmazer-Hanke DM. 68.  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. 505:3268–91 [Google Scholar]
  69. Schwaber JS, Sternini C, Brecha NC, Rogers WT, Card JP. 69.  1988. Neurons containing calcitonin gene-related peptide in the parabrachial nucleus project to the central nucleus of the amygdala. J. Comp. Neurol. 270:3416–26 [Google Scholar]
  70. Shor-Posner G, Azar AP, Insinga S, Leibowitz SF. 70.  1985. Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions. Physiol. Behav. 35:6883–90 [Google Scholar]
  71. Michaud JL, Rosenquist T, May NR, Fan CM. 71.  1998. Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Genes Dev. 12:203264–75 [Google Scholar]
  72. Holder JL, Butte NF, Zinn AR. 72.  2000. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum. Mol. Genet. 9:1101–8 [Google Scholar]
  73. Shah BP, Vong L, Olson DP, Koda S, Krashes MJ. 73.  et al. 2014. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. PNAS 111:3613193–98 [Google Scholar]
  74. Rossi J, Balthasar N, Olson D, Scott M, Berglund E. 74.  et al. 2011. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 13:2195–204 [Google Scholar]
  75. Xu Y, Wu Z, Sun H, Zhu Y, Kim ER. 75.  et al. 2013. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab. 18:6860–70 [Google Scholar]
  76. Blevins JE, Eakin TJ, Murphy JA, Schwartz MW, Baskin DG. 76.  2003. Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin. Brain Res. 993:1–230–41 [Google Scholar]
  77. Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR. 77.  2008. Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Mol. Endocrinol. 22:71723–34 [Google Scholar]
  78. Takayanagi Y, Kasahara Y, Onaka T, Takahashi N, Kawada T, Nishimori K. 78.  2008. Oxytocin receptor–deficient mice developed late-onset obesity. NeuroReport 19:9951–55 [Google Scholar]
  79. Camerino C. 79.  2009. Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity 17:5980–84 [Google Scholar]
  80. Wu Z, Xu Y, Zhu Y, Sutton AK, Zhao R. 80.  et al. 2012. An obligate role of oxytocin neurons in diet induced energy expenditure. PLOS ONE 7:9e45167 [Google Scholar]
  81. Biag J, Huang Y, Gou L, Hintiryan H, Askarinam A. 81.  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. 520:16–33 [Google Scholar]
  82. Sawchenko PE, Swanson LW. 82.  1983. The organization and biochemical specificity of afferent projections to the paraventricular and supraoptic nuclei. Prog. Brain Res. 60:19–29 [Google Scholar]
  83. Ziegler DR, Edwards MR, Ulrich-Lai YM, Herman JP, Cullinan WE. 83.  2012. Brainstem origins of glutamatergic innervation of the rat hypothalamic paraventricular nucleus. J. Comp. Neurol. 520:112369–94 [Google Scholar]
  84. Ulrich-Lai YM, Jones KR, Ziegler DR, Cullinan WE, Herman JP. 84.  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. 519:71301–19 [Google Scholar]
  85. Herman JP, Tasker JG, Ziegler DR, Cullinan WE. 85.  2002. Local circuit regulation of paraventricular nucleus stress integration: glutamate-GABA connections. Pharmacol. Biochem. Behav. 71:3457–68 [Google Scholar]
  86. Boudaba C, Schrader LA, Tasker JG. 86.  1997. Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus. J. Neurophysiol. 77:63396–400 [Google Scholar]
  87. Ziegler DR, Herman JP. 87.  2000. Local integration of glutamate signaling in the hypothalamic paraventricular region: regulation of glucocorticoid stress responses. Endocrinology 141:124801–4 [Google Scholar]
  88. Krashes MJ, Shah BP, Madara JC, Olson DP, Strochlic DE. 88.  et al. 2014. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature 507:7491238–42 [Google Scholar]
  89. Xi D, Gandhi N, Lai M, Kublaoui BM. 89.  2012. Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. PLOS ONE 7:4e36453 [Google Scholar]
  90. Tolson KP, Gemelli T, Meyer D, Yazdani U, Kozlitina J, Zinn AR. 90.  2014. Inducible neuronal inactivation of Sim1 in adult mice causes hyperphagic obesity. Endocrinology 155:72436–44 [Google Scholar]
  91. Madden CJ, Morrison SF. 91.  2009. Neurons in the paraventricular nucleus of the hypothalamus inhibit sympathetic outflow to brown adipose tissue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296:3R831–43 [Google Scholar]
  92. Bamshad M, Song CK, Bartness TJ. 92.  1999. CNS origins of the sympathetic nervous system outflow to brown adipose tissue. Am. J. Physiol. Regul. Integr. Comp. Physiol. 276:6, Part 2R1569–78 [Google Scholar]
  93. Caverson MM, Ciriello J, Calaresu FR. 93.  1984. Paraventricular nucleus of the hypothalamus: an electrophysiological investigation of neurons projecting directly to intermediolateral nucleus in the cat. Brain Res. 305:2380–83 [Google Scholar]
  94. Cao W-H, Madden CJ, Morrison SF. 94.  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. 299:1R277–90 [Google Scholar]
  95. Morrison SF, Madden CJ, Tupone D. 95.  2014. Central neural regulation of brown adipose tissue thermogenesis and energy expenditure. Cell Metab. 19:5741–56 [Google Scholar]
  96. Kong D, Tong Q, Ye C, Koda S, Fuller PM. 96.  et al. 2012. GABAergic RIP-Cre neurons in the arcuate nucleus selectively regulate energy expenditure. Cell 151:3645–57 [Google Scholar]
  97. Dodd GT, Decherf S, Loh K, Simonds SE, Wiede F. 97.  et al. 2015. Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell 160:1–288–104 [Google Scholar]
  98. Enriori PJ, Sinnayah P, Simonds SE, Garcia Rudaz C, Cowley MA. 98.  2011. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J. Neurosci. 31:3412189–97 [Google Scholar]
  99. Lindberg D, Chen P, Li C. 99.  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. 521:143167–90 [Google Scholar]
/content/journals/10.1146/annurev-physiol-021115-105347
Loading
/content/journals/10.1146/annurev-physiol-021115-105347
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error