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Developmental programming of hypothalamic melanocortin circuits

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The melanocortin system plays a critical role in the central regulation of food intake and energy balance. This system consists of neurons producing pro-opiomelanocortin (POMC), melanocortin receptors (MC4Rs), and the endogenous antagonist agouti-related peptide (AgRP). Pomc and Mc4r deficiency in rodents and humans causes early onset of obesity, whereas a loss of Agrp function is associated with leanness. Accumulating evidence shows that many chronic diseases, including obesity, might originate during early life. The melanocortin system develops during a relatively long period beginning during embryonic life with the birth of POMC and AgRP neurons and continuing postnatally with the assembly of their neuronal circuitry. The development of the melanocortin system requires the tight temporal regulation of molecular factors, such as transcription factors and axon guidance molecules, and cellular mechanisms, such as autophagy. It also involves a complex interplay of endocrine and nutritional factors. The disruption of one or more of these developmental factors can lead to abnormal maturation and function of the melanocortin system and has profound metabolic consequences later in life.

Abstract

The melanocortin system plays a critical role in the central regulation of food intake and energy balance. This system consists of neurons producing pro-opiomelanocortin (POMC), melanocortin receptors (MC4Rs), and the endogenous antagonist agouti-related peptide (AgRP). Pomc and Mc4r deficiency in rodents and humans causes early onset of obesity, whereas a loss of Agrp function is associated with leanness. Accumulating evidence shows that many chronic diseases, including obesity, might originate during early life. The melanocortin system develops during a relatively long period beginning during embryonic life with the birth of POMC and AgRP neurons and continuing postnatally with the assembly of their neuronal circuitry. The development of the melanocortin system requires the tight temporal regulation of molecular factors, such as transcription factors and axon guidance molecules, and cellular mechanisms, such as autophagy. It also involves a complex interplay of endocrine and nutritional factors. The disruption of one or more of these developmental factors can lead to abnormal maturation and function of the melanocortin system and has profound metabolic consequences later in life.

참고문헌 (107)

  1. Poggioli, R., "ACTH-(1-24)and alpha-MSH antagonize feeding behavior stimulated by kappa opiate agonists", Peptides, 7, pp.843~848 (1986)
  2. Belgardt, B. F., "CNS leptin and insulin action in the control of energy homeostasis", Ann. NY Acad. Sci, 1212, pp.97~113 (2010)
  3. Williams, K. W., "From neuroanatomy to behavior : central integration of peripheral signals regulating feeding behavior", Nat. Neurosci, 15, pp.1350~1355 (2012)
  4. Aponte, Y., "AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training", Nat. Neurosci, 14, pp.351~355 (2011)
  5. Zhan, C., "Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively", J. Neurosci, 33, pp.3624~3632 (2013)
  6. Luquet, S., "NPY", AgRP neurons are essential for feeding in adult mice but can be ablated in neonates, 2005, pp.310, 683~685
  7. Gropp, E., "Agouti-related peptide-expressing neurons are mandatory for feeding", Nat. Neurosci, 8, pp.1289~1291 (2005)
  8. Mountjoy, K. G., "Localization of the melanocortin-4 receptor(MC4-R)in neuroendocrine and autonomic control circuits in the brain", Mol. Endocrinol, 8, pp.1298~1308 (1994)
  9. Kishi, T., "Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat", J. Comp. Neurol, 457, pp.213~235 (2003)
  10. Liu, H., "Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter", J. Neurosci, 23, pp.7143~7154 (2003)
  11. Lu, X. Y., "Interaction between alphamelanocyte-stimulating hormone and corticotropin-releasing hormone in the regulation of feeding and hypothalamo-pituitary-adrenal responses", J. Neurosci, 23, pp.7863~7872 (2003)
  12. Coll, A. P., "The hormonal control of food intake", Cell, 129, pp.251~262 (2007)
  13. Sauer, F. C., "Mitosis in the neural tube", J. Comp. Neurol, 62, pp.377~405 (1935)
  14. thymidine autoradiographic study, "Neuropeptides", 1985, 477~480
  15. Padilla, S. L., "Pomc-expressing progenitors give rise to antagonistic neuronal populations in hypothalamic feeding circuits", Nat. Med, 16, pp.403~405 (2010)
  16. Bouret, S. G., "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, pp.2797~2805 (2004)
  17. Grove, K. L., "Postnatal development of the hypothalamic neuropeptide Y system", Neuroscience, 116, pp.393~406 (2003)
  18. Nilsson, I., "Maturation of the hypothalamic arcuate agouti-related protein system during postnatal development in the mouse", Dev. Brain Res, 155, pp.147~154 (2005)
  19. Mountjoy, K. G., "Melanocortin-4 receptor mRNA expression in the developing autonomic and central nervous systems", Dev. Brain Res, 107, pp.309~314 (1998)
  20. Glavas, M. M., "Melanocortinergic activation by Melanotan II inhibits feeding and increases uncoupling protein 1 messenger ribonucleic acid in the developing rat", Endocrinology, 148, pp.3279~3287 (2007)
  21. Melnick, I., "Developmental switch in neuropeptide Y and melanocortin effects in the paraventricular nucleus of the hypothalamus", Neuron, 56, pp.1103~1115 (2007)
  22. Grayson, B. E., "Prenatal development of hypothalamic neuropeptide systems in the nonhuman primate", Neuroscience, 143, pp.975~986 (2006)
  23. Koutcherov, Y., "Organization of human hypothalamus in fetal development", J. Comp. Neurol, 446, pp.301~324 (2002)
  24. Zhang, Y., "Position cloning of the mouse obese gene and its human homologue", Nature, 372, pp.425~ (1994)
  25. Kojima, M., "Ghrelin is a growth-hormone-releasing acylated peptide from stomach", Nature, 402, pp.656~660 (1999)
  26. Nakazato, M., "A role for ghrelin in the central regulation of feeding", Nature, 409, pp.194~198 (2001)
  27. Halaas, J. L., "Weight-reducing effects of the plasma protein encoded by the obese gene", Science, 269, pp.543~546 (1995)
  28. Pelleymounter, M., "Effects of the obese gene product on body weight regulation in ob", ob mice, 1995, pp.269, 540~543
  29. Campfield, L. A., "Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks", Science, 269, pp.546~549 (1995)
  30. Ahima, R., "Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function", J. Clin. Invest, 101, pp.1020~1027 (1998)
  31. Ahima, R. S., "Postnatal regulation of hypothalamic neuropeptide expression by leptin : implications for energy balance and body weight regulation", Regul. Pept, 92, pp.1~7 (2000)
  32. Proulx, K., "Leptin Regulates Appetite-Related Neuropeptides in the Hypothalamus of Developing Rats without Affecting Food Intake", Endocrinology, 143, pp.4683~4692 (2002)
  33. Mistry, A., "Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice", Am. J. Physiol, 277, pp.R742~R747 (1999)
  34. Schmidt, I., "The effect of leptin treatment on the development of obesity in overfed suckling Wistar rats", Int. J. Obes. Relat. Metab. Disord, 25, pp.1168~1174 (2001)
  35. Bouret, S. G., "Trophic action of leptin on hypothalamic neurons that regulate feeding", Science, 304, pp.108~110 (2004)
  36. Kamitakahara, A., "A critical period for the trophic actions of leptin on AgRP neurons in the arcuate nucleus of the hypothalamus", J. Comp. Neurol, 526, pp.133~145 (2017)
  37. Caron, E., "Distribution of leptin-sensitive cells in the postnatal and adult mouse brain", J. Comp. Neurol, 518, pp.459~476 (2010)
  38. Bouret, S. G., "Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits", J. Neurosci, 32, pp.1244~1252 (2012)
  39. Bouret, S., "Development of leptin-sensitive circuits", J. Neuroendocrinol, 19, pp.575~582 (2007)
  40. Tschöp, M., "Ghrelin induces adiposity in rodent", Nature, 407, pp.908~913 (2000)
  41. Cowley, M. A., "The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuits regulating energy homeostasis", Neuron, 37, pp.649~661 (2003)
  42. Piao, H., "Ghrelin stimulates milk intake by affecting adult type feeding behaviour in postnatal rats", J. Neuroendocrinol, 20, pp.330~334 (2008)
  43. Steculorum, S. M., "Ghrelin programs development of hypothalamic feeding circuits", J. Clin. Invest, 125, pp.846~858 (2015)
  44. Tolle, V., "In vivo and in vitro effects of ghrelin", motilin-related peptide on growth hormone secretion in the rat, 2001, pp.73, 54~61
  45. Wasinski, F., "Growth hormone receptor deletion reduces the density of axonal projections from hypothalamic arcuate nucleus neurons", Neuroscience, 434, pp.136~147 (2020)
  46. Drucker, D. J., "Glucagon-like peptides", Diabetes, 47, pp.159~169 (1998)
  47. Rozo, A. V., "Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture", Mol. Metab, 6, pp.748~759 (2017)
  48. Li, C., "Amylin receptor insensitivity impairs hypothalamic POMC neuron differentiation in the male offspring of maternal high-fat diet-fed mice", Mol. Metab, 44, pp.101135~ (2020)
  49. Abegg, K., "Involvement of amylin and leptin in the development of projections from the area postrema to the nucleus of the solitary tract", Front. Endocrinol. (Lausanne), 8, pp.324~ (2017)
  50. Lutz, T. A., "Amylin selectively signals onto POMC neurons in the arcuate nucleus of the hypothalamus", Diabetes, 67, pp.805~817 (2018)
  51. Kimura, S., "The T", ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary, 1996, pp.10, 60~69
  52. Acampora, D., "Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene", Genes Dev, 13, pp.2787~2800 (1999)
  53. Wang, W., "The murine Otp homeobox gene plays an essential role in the specification of neuronal cell lineages in the developing hypothalamus", Dev. Biol, 227, pp.432~449 (2000)
  54. Marín, O., "Patterning of the basal telencephalon and hypothalamus is essential for guidance of cortical projections", Development, 129, pp.761~773 (2002)
  55. Sussel, L., "Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum", Development, 126, pp.3359~3370 (1999)
  56. Yee, C. L., "Arcuate nucleus expression of NKX2.1 and DLX and lineages expressing these transcription factors in neuropeptide Y+, proopiomelanocortin+, and tyrosine hydroxylase+ neurons in neonatal and adult mice", J. Comp. Neurol, 517, pp.37~50 (2009)
  57. Orquera, D. P., "The homeodomain transcription factor NKX2.1 Is essential for the early specification of melanocortin neuron identity and activates Pomc expression in the developing hypothalamus", J. Neurosci, 39, pp.4023~4035 (2019)
  58. Nasif, S., "Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood", Proc. Natl Acad. Sci. USA, 112, pp.E1861~E1870 (2015)
  59. Lee, B., "The LIM-homeobox transcription factor Isl1 plays crucial roles in the development of multiple arcuate nucleus neurons", Development, 143, pp.3763~3773 (2016)
  60. Lee, B., "Dlx1", 2 and Otp coordinate the production of hypothalamic GHRH-and AgRP-neurons, 2018, pp.9, 2026~
  61. Hu, Y., "Development and characterization of an Otp conditional loss of function allele", Genesis, 58, pp.e23370~ (2020)
  62. Manning, L., "Regional morphogenesis in the hypothalamus : a BMP-Tbx2pathway coordinates fate and proliferation through Shh downregulation", Dev. Cell, 11, pp.873~885 (2006)
  63. Shimogori, T., "A genomic atlas of mouse hypothalamic development", Nat. Neurosci, 13, pp.767~775 (2010)
  64. Lagutin, O. V., "Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development", Genes Dev, 17, pp.368~379 (2003)
  65. Geng, X., "Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly", Dev. Cell, 15, pp.236~247 (2008)
  66. Lu, F., "Rax is a selector gene for mediobasal hypothalamic cell types", J. Neurosci, 33, pp.259~272 (2013)
  67. Takebayashi, H., "Dynamic expression of basic helix-loop-helix Olig family members: implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3", Mech. Dev, 99, pp.143~148 (2000)
  68. Zhou, Q., "Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors", Neuron, 25, pp.331~343 (2000)
  69. Peng, C. Y., "BMP receptor 1A regulates development of hypothalamic circuits critical for feeding behavior", J. Neurosci, 32, pp.17211~17224 (2012)
  70. Pelling, M., "Differential requirements for neurogenin 3 in the development of POMC and NPY neurons in the hypothalamus", Dev. Biol, 349, pp.406~416 (2011)
  71. Anthwal, N., "Conditional deletion of neurogenin-3 using Nkx2.1iCre results in a mouse model for the central control of feeding, activity and obesity", Dis. Model. Mech, 6, pp.1133~1145 (2013)
  72. McNay, D. E. G., "Mash1 is required for generic and subtype differentiation of hypothalamic neuroendocrine cells", Mol. Endocrinol, 20, pp.1623~1632 (2006)
  73. Aujla, P. K., "Notch", Rbpjκ signaling regulates progenitor maintenance and differentiation of hypothalamic arcuate neurons, 2013, pp.140, 3511~3521
  74. Croizier, S., "Central Dicer-miR-103", 107controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis, 2018, pp.7, e40429~
  75. Quarta, C., "Functional identity of hypothalamic melanocortin neurons depends on Tbx3", Nat. Metab, 1, pp.222~235 (2019)
  76. Tessier-Lavigne, M., "The molecular biology of axon guidance", Science, 274, pp.1123~1133 (1996)
  77. van der Klaauw, A. A., "Human Semaphorin 3 variants link melanocortin circuit development and energy balance", Cell, 176, pp.729~742.e718 (2019)
  78. Gervais, M., "EphrinB1modulates glutamatergic inputs into POMC-expressing progenitors and controls glucose homeostasis", PLoS Biol, 18, pp.e3000680~ (2020)
  79. Nilsson, I., "Maturation of the hypothalamic arcuate agouti-related protein system during postnatal development in the mouse", Dev. Brain Res, 155, pp.147~154 (2005)
  80. Klionsky, D. J., "Autophagy : from phenomenology to molecular understanding in less than a decade", Nat. Rev. Mol. Cell Biol, 8, pp.931~937 (2007)
  81. Komatsu, M., "Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice", J. Cell Biol, 169, pp.425~434 (2005)
  82. Coupe, B., "Loss of autophagy in pro-opiomelanocortin neurons perturbs axon growth and causes metabolic dysregulation", Cell Metab, 15, pp.247~255 (2012)
  83. Park, S., "The endoplasmic reticulum stress-autophagy pathway controls hypothalamic development and energy balance regulation in leptin-deficient neonates", Nat. Commun, 11, pp.1914~ (2020)
  84. Fuchs, J. L., "Neuronal primary cilia : a review", Cell Biol. Int, 28, pp.111~118 (2004)
  85. Carreno, G., "Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3", LHX4 pituitary embryonic precursors, 2017, pp.144, 3289~3302
  86. Lee, C. H., "Primary cilia mediate early life programming of adiposity through lysosomal regulation in the developing mouse hypothalamus", Nat. Commun, 11, pp.5772~ (2020)
  87. Siljee, J. E., "Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity", Nat. Genet, 50, pp.180~ (2018)
  88. Chen, H., "Hypothalamic neuroendocrine circuitry is programmed by maternal obesity : interaction with postnatal nutritional environment", PLoS ONE, 4, pp.e6259~ (2009)
  89. Kirk, S. L., "Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring", PLoS ONE, 4, pp.e5870~ (2009)
  90. Vogt, M. C., "Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding", Cell, 156, pp.495~509 (2014)
  91. Park, S., "Maternal obesity-induced endoplasmic reticulum stress causes metabolic alterations and abnormal hypothalamic development in the offspring", PLoS Biol, 18, pp.e3000296~ (2020)
  92. Haddad-Tóvolli, R., "Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming in mice", Mol. Metab, 36, pp.100963~ (2020)
  93. Sullivan, E. L., "Maternal and postnatal high-fat diet consumption programs energy balance and hypothalamic melanocortin signaling in nonhuman primate offspring", Am. J. Physiol. Regul. Integr. Comp. Physiol, 313, pp.R169~r179 (2017)
  94. Levin, B. E., "Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats", Am. J. Physiol. Regul. Integr. Comp. Physiol, 273, pp.R725~R730 (1997)
  95. Bouret, S. G., "Hypothalamic neural projections are permanently disrupted in diet-induced obese rats", Cell Metab, 7, pp.179~185 (2008)
  96. Horvath, T. L., "Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity", Proc. Natl Acad. Sci. USA, 107, pp.14875~14880 (2010)
  97. Dearden, L., "Maternal obesity causes fetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways", Mol. Metab, 42, pp.101079~ (2020)
  98. Johnson, M. D., "Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred dietinduced obese rat", Am. J. Physiol. Regul. Integr. Comp. Physiol, 311, pp.R1032~R1044 (2016)
  99. Kennedy, G. C., "The development with age of hypothalamic restraint upon the appetite of the rat", J. Endocrinol, 16, pp.9~17 (1957)
  100. Widdowson, E. M., "Some effects of accelerating growth. I. General somatic development", Proc. R. Soc. Lond. B Biol. Sci, 152, pp.188~206 (1960)
  101. Glavas, M. M., "Early overnutrition results in early-onset arcuate leptin resistance and increased sensitivity to high-fat diet", Endocrinology, 151, pp.1598~1610 (2010)
  102. Roberts, B. L., "Early overnutrition alters synaptic signaling and induces leptin resistance in arcuate proopiomelanocortin neurons", Physiol. Behav, 206, pp.166~174 (2019)
  103. Collden, G., "Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin", Mol. Metab, 4, pp.15~24 (2015)
  104. Srinivasan, M., "A high-carbohydrate diet in the immediate postnatal life of rats induces adaptations predisposing to adult-onset obesity", J. Endocrinol, 197, pp.565~574 (2008)
  105. Plagemann, A., "Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding : an epigenetic model of obesity and the metabolic syndrome", J. Physiol, 587, pp.4963~4976 (2009)
  106. Kuehnen, P., "An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity", PLoS Genet, 8, pp.e1002543~ (2012)
  107. Davidowa, H., "Altered responses to orexigenic(AGRP, MCH)and anorexigenic(a-MSH, CART)neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats", Eur. J. Neurosci, 18, pp.613~621 (2003)

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