The role of astrocytes in the hypothalamic response and adaptation to metabolic signals

Progress in Neurobiology

Volumn 144, Issue , 2016, Pages 68-87

  Chowen, Julie A ^a   Argente Arizón, Pilar ^a,b   Freire Regatillo, Alejandra ^a,b   Frago, Laura M ^a,b   Horvath, Tamas L ^c   Argente, Jesús ^a,b  

^a INSTITUTO DE SALUD CARLOS III   (Spain)

^b UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Glia; High fat diet; Hypothalamic inflammation; Leptin; Melanocortin system; Synaptic plasticity

Indexed keywords

ESTROGEN; FATTY ACID; GHRELIN; GLUCOSE; LEPTIN; LEPTIN RECEPTOR; NEUROPEPTIDE; OXYTOCIN; VASOPRESSIN;

ASTROCYTE; ASTROCYTOSIS; BRAIN CAPILLARY; CELL POPULATION; CIRCADIAN RHYTHM; DIET RESTRICTION; ENERGY BALANCE; ENVIRONMENTAL IMPACT; GLIA CELL; HEREDITY; HORMONE TRANSPORT; HUMAN; HYPOTHALAMUS; METABOLISM; NERVE CELL PLASTICITY; NEUROENDOCRINE SYSTEM; NONHUMAN; NUTRITION; OBESITY; OSMOSIS; PRIORITY JOURNAL; REPRODUCTION; REVIEW; SEX DIFFERENCE; SIGNAL TRANSDUCTION; ANIMAL; NON INSULIN DEPENDENT DIABETES MELLITUS; PHYSIOLOGY;

ANIMALS; ASTROCYTES; DIABETES MELLITUS, TYPE 2; HUMANS; HYPOTHALAMUS; OBESITY; SIGNAL TRANSDUCTION;

EID: 84961806552     PISSN: 03010082     EISSN: 18735118     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2016.03.001     Document Type: Review

References (255)

1. Ahima, R.S., Bjorbaek, C., Osei, S., Flier, J.S., Regulation of neuronal and glial proteins by leptin: implications for brain development. Endocrinology 140 (1999), 2755–2762.
2. Ainge, H., Thompson, C., Ozanne, S.E., Rooney, K.B., A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int. J. Obes. (Lond.) 35 (2011), 325–335.
3. Allard, C., Carneiro, L., Grall, S., Cline, B.H., Fioramonti, X., Chretien, C., Baba-Aissa, F., Giaume, C., Penicaud, L., Leloup, C., Hypothalamic astroglial connexins are required for brain glucose sensing-induced insulin secretion. J. Cereb. Blood Flow Metab. 34 (2014), 339–346.
4. Anand, B.K., Chhina, G.S., Sharma, K.N., Dua, S., Singh, B., Activity of single neurons in the hypothalamic feeding centers: effect of glucose. Am. J. Physiol. 207 (1964), 1146–1154.
5. Anderson, C.M., Swanson, R.A., Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32 (2000), 1–14.
6. Araque, A., Parpura, V., Sanzgiri, R.P., Haydon, P.G., Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur. J. Neurosci. 10:6 (1998), 2129–2142.
7. Araque, A., Sanzgiri, R.P., Parpura, V., Haydon, P.G., Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. J. Neurosci. 18 (1998), 6822–6829.
8. Arble, D.M., Bass, J., Laposky, A.D., Vitaterna, M.H., Turek, F.W., Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 17 (2009), 2100–2102.
9. Argente-Arizon, P., Freire-Regatillo, A., Argente, J., Chowen, J.A., Role of non-neuronal cells in body weight and appetite control. Front. Endocrinol. (Lausanne), 6, 2015, 42.
10. Auestad, N., Korsak, R.A., Morrow, J.W., Edmond, J., Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J. Neurochem. 56 (1991), 1376–1386.
11. Azcoitia, I., Garcia-Ovejero, D., Chowen, J.A., Garcia-Segura, L.M., Astroglia play a key role in the neuroprotective actions of estrogen. Prog. Brain Res. 132 (2001), 469–478.
12. Bady, I., Marty, N., Dallaporta, M., Emery, M., Gyger, J., Tarussio, D., Foretz, M., Thorens, B., Evidence from glut2-null mice that glucose is a critical physiological regulator of feeding. Diabetes 55:6 (2006), 988–995.
13. Balthasar, N., Coppari, R., McMinn, J., Liu, S.M., Lee, C.E., Tang, V., Kenny, C.D., McGovern, R.A., Chua, S.C. Jr., Elmquist, J.K., Lowell, B.B., Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42 (2004), 983–991.
14. Balland, E., Dam, J., Langlet, F., Caron, E., Steculorum, S., Messina, A., Rasika, S., Falluel-Morel, A., Anouar, Y., Dehouck, B., Trinquet, E., Jockers, R., Bouret, S.G., Prevot, V., Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab. 19 (2014), 293–301.
15. Banks, W.A., Coon, A.B., Robinson, S.M., Moinuddin, A., Shultz, J.M., Nakaoke, R., Morley, J.E., Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 53 (2004), 1253–1260.
16. Banks, W.A., Farrell, C.L., Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am. J. Physiol. Endocrinol. Metab. 285 (2003), E10–15.
17. Banks, W.A., Kastin, A.J., Huang, W., Jaspan, J.B., Maness, L.M., Leptin enters the brain by a saturable system independent of insulin. Peptides 17 (1996), 305–311.
18. Baquedano, E., Chowen, J.A., Argente, J., Frago, L.M., Differential effects of GH and GH-releasing peptide-6 on astrocytes. J. Endocr. 218 (2013), 263–274.
19. Barker, D.J., Obesity and early life. Obes. Rev. 8:suppl. 1 (2007), 45–49.
20. Baroncini, M., Allet, C., Leroy, D., Beauvillain, J.C., Francke, J.P., Prevot, V., Morphological evidence for direct interaction between gonadotrophin-releasing hormone neurones and astroglial cells in the human hypothalamus. J. Neuroendocrinol. 19 (2007), 691–702.
21. Barr, V.A., Lane, K., Taylor, S.I., Subcellular localization and internalization of the four human leptin receptor isoforms. J. Biol. Chem. 274 (1999), 21416–21424.
22. Baumann, H., Morella, K.K., White, D.W., Dembski, M., Bailon, P.S., Kim, H., Lai, C.F., Tartaglia, L.A., The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. U. S. A. 93 (1996), 8374–8378.
23. Belanger, M., Allaman, I., Magistretti, P.J., Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14 (2011), 724–738.
24. Bellefontaine, N., Hanchate, N.K., Parkash, J., Campagne, C., de Seranno, S., Clasadonte, J., d'Anglemont de Tassigny, X., Prevot, V., Nitric oxide as key mediator of neuron-to-neuron and endothelia-to-glia communication involved in the neuroendocrine control of reproduction. Neuroendocrinology 93 (2011), 74–89.
25. Benani, A., Hryhorczuk, C., Gouaze, A., Fioramonti, X., Brenachot, X., Guissard, C., Krezymon, A., Duparc, T., Colom, A., Nedelec, E., Rigault, C., Lemoine, A., Gascuel, J., Gerardy-Schahn, R., Valet, P., Knauf, C., Lorsignol, A., Penicaud, L., Food intake adaptation to dietary fat involves PSA-dependent rewiring of the arcuate melanocortin system in mice. J. Neurosci. 32 (2012), 11970–11979.
26. Benzler, J., Ganjam, G.K., Pretz, D., Oelkrug, R., Koch, C.E., Legler, K., Stohr, S., Culmsee, C., Williams, L.M., Tups, A., Central inhibition of IKKbeta/NF-kappaB signaling attenuates high-fat diet-induced obesity and glucose intolerance. Diabetes 64 (2015), 2015–2027.
27. Bhutia, S.K., Kegelman, T.P., Das, S.K., Azab, B., Su, Z.Z., Lee, S.G., Sarkar, D., Fisher, P.B., Astrocyte elevated gene-1 induces protective autophagy. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 22243–22248.
28. Blázquez, C., Woods, A., De Ceballos, M.L., Carling, D., Guzmán, M., The AMP-activated protein kinase is involved in the regulation of ketone body production by astrocytes. J. Neurochem. 73 (1999), 1674–1682.
29. Bonfanti, L., Theodosis, D.T., Polysialic acid and activity-dependent synapse remodeling. Cell. Adh. Migr. 3 (2009), 43–50.
30. Bonfardin, V.D., Fossat, P., Theodosis, D.T., Oliet, S.H., Glia-dependent switch of kainate receptor presynaptic action. J. Neurosci. 30 (2010), 985–995.
31. Bosier, B., Bellocchio, L., Metna-Laurent, M., Soria-Gomez, E., Matias, I., Hebert-Chatelain, E., Cannich, A., Maitre, M., Leste-Lasserre, T., Cardinal, P., Mendizabal-Zubiaga, J., Canduela, M.J., Reguero, L., Hermans, E., Grandes, P., Cota, D., Marsicano, G., Astroglial CB1 cannabinoid receptors regulate leptin signaling in mouse brain astrocytes. Mol. Metab. 2 (2013), 393–404.
32. Bouret, S.G., Draper, S.J., Simerly, R.B., Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304 (2004), 108–110.
33. Bouret, S.G., Gorski, J.N., Patterson, C.M., Chen, S., Levin, B.E., Simerly, R.B., Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab. 7 (2008), 179–185.
34. Bouyakdan, K., Taib, B., Budry, L., Zhao, S., Rodaros, D., Neess, D., Mandrup, S., Faergeman, N.J., Alquier, T., A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes. J. Neurochem. 133 (2015), 253–265.
35. Boyles, J.K., Pitas, R.E., Wilson, E., Mahley, R.W., Taylor, J.M., Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J. Clin. Invest. 76 (1985), 1501–1513.
36. Bushong, E.A., Martone, M.E., Jones, Y.Z., Ellisman, M.H., Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci. 22 (2002), 183–192.
37. Cai, D., Neuroinflammation and neurodegeneration in overnutrition-induced diseases. Trends Endocrinol. Metab. 24 (2013), 40–47.
38. Candib, L.M., Obesity and diabetes in vulnerable populations: reflection on proximal and distal causes. Ann. Fam. Med. 5 (2007), 547–556.
39. Cardona-Gomez, G.P., DonCarlos, L., Garcia-Segura, L.M., Insulin-like growth factor I receptors and estrogen receptors colocalize in female rat brain. Neuroscience 99 (2000), 751–760.
40. Caruso, C., Carniglia, L., Durand, D., Scimonelli, T.N., Lasaga, M., Astrocytes: new targets of melanocortin 4 receptor actions. J. Mol. Endocrinol. 51 (2013), R33–50.
41. Claret, M., Smith, M.A., Batterham, R.L., Selman, C., Choudhury, A.I., Fryer, L.G., Clements, M., Al-Qassab, H., Heffron, H., Xu, A.W., Speakman, J.R., Barsh, G.S., Viollet, B., Vaulont, S., Ashford, M.L., Carling, D., Withers, D.J., AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J. Clin. Invest. 117 (2007), 2325–2336.
42. Clasadonte, J., Poulain, P., Hanchate, N.K., Corfas, G., Ojeda, S.R., Prevot, V., Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 16104–16109.
43. Collden, G., Balland, E., Parkash, J., Caron, E., Langlet, F., Prevot, V., Bouret, S.G., Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin. Mol. Metab. 4 (2015), 15–24.
44. Compere, V., Lanfray, D., Castel, H., Morin, F., Leprince, J., Dureuil, B., Vaudry, H., Pelletier, G., Tonon, M.C., Acute food deprivation reduces expression of diazepam-binding inhibitorthe precursor of the anorexigenic octadecaneuropeptide ODN, in mouse glial cells. J. Mol. Endocrinol. 44 (2010), 295–299.
45. Compere, V., Li, S., Leprince, J., Tonon, M.C., Vaudry, H., Pelletier, G., Effect of intracerebroventricular administration of the octadecaneuropeptide on the expression of pro-opiomelanocortin, neuropeptide Y and corticotropin-releasing hormone mRNAs in rat hypothalamus. J. Neuroendocrinol. 15 (2003), 197–203.
46. Cone, R.D., Studies on the physiological functions of the melanocortin system. Endocr. Rev. 27 (2006), 736–749.
47. Cone, R.D., Cowley, M.A., Butler, A.A., Fan, W., Marks, D.L., Low, M.J., The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int. J. Obes. Relat. Metab. Disord. 25:suppl. 5 (2001), S63–S67.
48. Cowley, M.A., Smart, J.L., Rubinstein, M., Cerdan, M.G., Diano, S., Horvath, T.L., Cone, R.D., Low, M.J., Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411 (2001), 480–484.
49. Cowley, M.A., Smith, R.G., Diano, S., Tschop, M., Pronchuk, N., Grove, K.L., Strasburger, C.J., Bidlingmaier, M., Esterman, M., Heiman, M.L., Garcia-Segura, L.M., Nillni, E.A., Mendez, P., Low, M.J., Sotonyi, P., Friedman, J.M., Liu, H., Pinto, S., Colmers, W.F., Cone, R.D., Horvath, T.L., The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37 (2003), 649–661.
50. Cristiano, L., Cimini, A., Moreno, S., Ragnelli, A.M., Paola Ceru, M., Peroxisome proliferator-activated receptors (PPARs) and related transcription factors in differentiating astrocyte cultures. Neuroscience 131 (2005), 577–587.
51. Csakvari, E., Hoyk, Z., Gyenes, A., Garcia-Ovejero, D., Garcia-Segura, L.M., Parducz, A., Fluctuation of synapse density in the arcuate nucleus during the estrous cycle. Neuroscience 144 (2007), 1288–1292.
52. Csakvari, E., Kurunczi, A., Hoyk, Z., Gyenes, A., Naftolin, F., Parducz, A., Estradiol-induced synaptic remodeling of tyrosine hydroxylase immunopositive neurons in the rat arcuate nucleus. Endocrinology 149 (2008), 4137–4141.
53. Chang, G.Q., Gaysinskaya, V., Karatayev, O., Leibowitz, S.F., Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J. Neurosci. 28 (2008), 12107–12119.
54. Chari, M., Yang, C.S., Lam, C.K., Lee, K., Mighiu, P., Kokorovic, A., Cheung, G.W., Lai, T.Y., Wang, P.Y., Lam, T.K., Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo. Diabetes 60 (2011), 1901–1906.
55. Chowen, J.A., Argente, J., Horvath, T.L., Uncovering novel roles of nonneuronal cells in body weight homeostasis and obesity. Endocrinology 154 (2013), 3001–3007.
56. Chowen, J.A., Busiguina, S., Garcia-Segura, L.M., Sexual dimorphism and sex steroid modulation of glial fibrillary acidic protein messenger RNA and immunoreactivity levels in the rat hypothalamus. Neuroscience 69 (1995), 519–532.
57. de Mateos-Verchere, J.G., Leprince, J., Tonon, M.C., Vaudry, H., Costentin, J., The octadecaneuropeptide [diazepam-binding inhibitor (33–50)] exerts potent anorexigenic effects in rodents. Eur. J. Pharmacol. 414 (2001), 225–231.
58. De Pitta, M., Brunel, N., Volterra, A., Astrocytes: orchestrating synaptic plasticity?. Neuroscience, 2015.
59. De Souza, C.T., Araujo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Saad, M.J., Velloso, L.A., Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146 (2005), 4192–4199.
60. Deleuze, C., Duvoid, A., Hussy, N., Properties and glial origin of osmotic-dependent release of taurine from the rat supraoptic nucleus. J. Physiol. 507:Pt 2 (1998), 463–471.
61. Denroche, H.C., Huynh, F.K., Kieffer, T.J., The role of leptin in glucose homeostasis. J. Diabetes. Invest. 3 (2012), 115–129.
62. Devos, R., Richards, J.G., Campfield, L.A., Tartaglia, L.A., Guisez, Y., van der Heyden, J., Travernier, J., Plaetinck, G., Burn, P., OB protein binds specifically to the choroid plexus of mice and rats. Proc. Natl. Acad. Sci. U. S. A. 93 (1996), 5668–5673.
63. Dezonne, R.S., Lima, F.R., Trentin, A.G., Gomes, F.C., Thyroid hormone and astroglia: endocrine control of the neural environment. J. Neuroendocrinol. 27 (2015), 435–445.
64. Diano, S., Kalra, S.P., Horvath, T.L., Leptin receptor immunoreactivity is associated with the Golgi apparatus of hypothalamic neurons and glial cells. J. Neuroendocrinol. 10 (1998), 647–650.
65. Dixit, V.D., Weeraratna, A.T., Yang, H., Bertak, D., Cooper-Jenkins, A., Riggins, G.J., Eberhart, C.G., Taub, D.D., Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility. J. Biol. Chem. 281 (2006), 16681–16690.
66. do Rego, J.C., Orta, M.H., Leprince, J., Tonon, M.C., Vaudry, H., Costentin, J., Pharmacological characterization of the receptor mediating the anorexigenic action of the octadecaneuropeptide: evidence for an endozepinergic tone regulating food intake. Neuropsychopharmacology 32 (2007), 1641–1648.
67. DonCarlos, L.L., Sarkey, S., Lorenz, B., Azcoitia, I., Garcia-Ovejero, D., Huppenbauer, C., Garcia-Segura, L.M., Novel cellular phenotypes and subcellular sites for androgen action in the forebrain. Neuroscience 138 (2006), 801–807.
68. Dorfman, M.D., Thaler, J.P., Hypothalamic inflammation and gliosis in obesity. Curr. Opin. Endocrinol. Diabetes Obes. 22 (2015), 325–330.
69. Eckhardt, M., Bukalo, O., Chazal, G., Wang, L., Goridis, C., Schachner, M., Gerardy-Schahn, R., Cremer, H., Dityatev, A., Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination of the roles of neural cell adhesion molecule protein and polysialic acid in neural development and synaptic plasticity. J. Neurosci. 20 (2000), 5234–5244.
70. Elias, C.F., Aschkenasi, C., Lee, C., Kelly, J., Ahima, R.S., Bjorbaek, C., Flier, J.S., Saper, C.B., Elmquist, J.K., Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron 23 (1999), 775–786.
71. Elias, C.F., Lee, C., Kelly, J., Aschkenasi, C., Ahima, R.S., Couceyro, P.R., Kuhar, M.J., Saper, C.B., Elmquist, J.K., Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21 (1998), 1375–1385.
72. Emmerzaal, T.L., Kiliaan, A.J., Gustafson, D.R., 2003–2013: a decade of body mass index, Alzheimer's disease, and dementia. J. Alzheimers Dis. 43 (2015), 739–755.
73. Farooqi, I.S., Wangensteen, T., Collins, S., Kimber, W., Matarese, G., Keogh, J.M., Lank, E., Bottomley, B., Lopez-Fernandez, J., Ferraz-Amaro, I., Dattani, M.T., Ercan, O., Myhre, A.G., Retterstol, L., Stanhope, R., Edge, J.A., McKenzie, S., Lessan, N., Ghodsi, M., De Rosa, V., Perna, F., Fontana, S., Barroso, I., Undlien, D.E., O'Rahilly, S., Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N. Engl. J. Med. 356 (2007), 237–247.
74. Fei, H., Okano, H.J., Li, C., Lee, G.H., Zhao, C., Darnell, R., Friedman, J.M., Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc. Natl. Acad. Sci. U. S. A. 94 (1997), 7001–7005.
75. Fernandez-Galaz, M.C., Morschl, E., Chowen, J.A., Torres-Aleman, I., Naftolin, F., Garcia-Segura, L.M., Role of astroglia and insulin-like growth factor-I in gonadal hormone-dependent synaptic plasticity. Brain Res. Bull. 44 (1997), 525–531.
76. Friedman, J.M., Halaas, J.L., Leptin and the regulation of body weight in mammals. Nature 395 (1998), 763–770.
77. Fuente-Martin, E., Garcia-Caceres, C., Diaz, F., Argente-Arizon, P., Granado, M., Barrios, V., Argente, J., Chowen, J.A., Hypothalamic inflammation without astrogliosis in response to high sucrose intake is modulated by neonatal nutrition in male rats. Endocrinology 154 (2013), 2318–2330.
78. Fuente-Martin, E., Garcia-Caceres, C., Granado, M., de Ceballos, M.L., Sanchez-Garrido, M.A., Sarman, B., Liu, Z.W., Dietrich, M.O., Tena-Sempere, M., Argente-Arizon, P., Diaz, F., Argente, J., Horvath, T.L., Chowen, J.A., Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J. Clin. Invest. 122 (2012), 3900–3913.
79. Fuente-Martin, E., Garcia-Caceres, C., Granado, M., Sanchez-Garrido, M.A., Tena-Sempere, M., Frago, L.M., Argente, J., Chowen, J.A., Early postnatal overnutrition increases adipose tissue accrual in response to a sucrose-enriched diet. Am. J. Physiol. Endocrinol. Metab. 302 (2012), E1586–1598.
80. Fuente-Martin, E., Garcia-Caceres, C., Morselli, E., Clegg, D.J., Chowen, J.A., Finan, B., Brinton, R.D., Tschop, M.H., Estrogen, astrocytes and the neuroendocrine control of metabolism. Rev. Endocr. Metab. Disord. 14 (2013), 331–338.
81. Fuente-Martin, E., Granado, M., Garcia-Caceres, C., Sanchez-Garrido, M.A., Frago, L.M., Tena-Sempere, M., Argente, J., Chowen, J.A., Early nutritional changes induce sexually dimorphic long-term effects on body weight gain and the response to sucrose intake in adult rats. Metabolism 61 (2012), 812–822.
82. Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C.S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C.A., Roberts, J.L., Gao, X.B., Mobbs, C., Shulman, G.I., Diano, S., Horvath, T.L., Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat. Med. 13 (2007), 89–94.
83. Gao, Y., Ottaway, N., Schriever, S.C., Legutko, B., Garcia-Caceres, C., de la Fuente, E., Mergen, C., Bour, S., Thaler, J.P., Seeley, R.J., Filosa, J., Stern, J.E., Perez-Tilve, D., Schwartz, M.W., Tschop, M.H., Yi, C.X., Hormones and diet but not body weight, control hypothalamic microglial activity. Glia 62 (2014), 17–25.
84. Garcia-Caceres, C., Fuente-Martin, E., Argente, J., Chowen, J.A., Emerging role of glial cells in the control of body weight. Mol. Metabol. 1 (2012), 37–46.
85. Garcia-Caceres, C., Fuente-Martin, E., Burgos-Ramos, E., Granado, M., Frago, L.M., Barrios, V., Horvath, T., Argente, J., Chowen, J.A., Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels. Endocrinology 152 (2011), 1809–1818.
86. Garcia-Caceres, C., Fuente-Martin, E., Diaz, F., Granado, M., Argente-Arizon, P., Frago, L.M., Freire-Regatillo, A., Barrios, V., Argente, J., Chowen, J.A., The opposing effects of ghrelin on hypothalamic and systemic inflammatory processes are modulated by its acylation status and food intake in male rats. Endocrinology 155 (2014), 2868–2880.
87. Garcia-Segura, L.M., Chowen, J.A., Naftolin, F., Endocrine glia: roles of glial cells in the brain actions of steroid and thyroid hormones and in the regulation of hormone secretion. Front. Neuroendocrinol. 17:6 (1996), 180–211.
88. Garcia-Segura, L.M., Chowen, J.A., Parducz, A., Naftolin, F., Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms. Prog. Neurobiol. 44 (1994), 279–307.
89. Garcia-Segura, L.M., Lorenz, B., DonCarlos, L.L., The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output. Reproduction 135 (2008), 419–429.
90. Giaume, C., Theis, M., Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system. Brain Res. Rev. 63 (2010), 160–176.
91. Gies, U., Theodosis, D.T., Synaptic plasticity in the rat supraoptic nucleus during lactation involves GABA innervation and oxytocin neurons: a quantitative immunocytochemical analysis. J. Neurosci. 14 (1994), 2861–2869.
92. Guillod-Maximin, E., Lorsignol, A., Alquier, T., Penicaud, L., Acute intracarotid glucose injection towards the brain induces specific c-fos activation in hypothalamic nuclei: involvement of astrocytes in cerebral glucose-sensing in rats. J. Neuroendocrinol. 16 (2004), 464–471.
93. Gupta, S., Knight, A.G., Gupta, S., Keller, J.N., Bruce-Keller, A.J., Saturated long-chain fatty acids activate inflammatory signaling in astrocytes. J. Neurochem. 120 (2012), 1060–1071.
94. Guzman, M., Blazquez, C., Is there an astrocyte-neuron ketone body shuttle?. Trends Endocrinol. Metab. 12 (2001), 169–173.
95. Gyengesi, E., Liu, Z.W., D'Agostino, G., Gan, G., Horvath, T.L., Gao, X.B., Diano, S., Corticosterone regulates synaptic input organization of POMC and NPY/AgRP neurons in adult mice. Endocrinology 151 (2010), 5395–5402.
96. Haber, M., Zhou, L., Murai, K.K., Cooperative astrocyte and dendritic spine dynamics at hippocampal excitatory synapses. J. Neurosci. 26 (2006), 8881–8891.
97. Hahn, T.M., Breininger, J.F., Baskin, D.G., Schwartz, M.W., Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat. Neurosci. 1 (1998), 271–272.
98. Halassa, M.M., Fellin, T., Haydon, P.G., Tripartite synapses: roles for astrocytic purines in the control of synaptic physiology and behavior. Neuropharmacology 57 (2009), 343–346.
99. Heine, P.A., Taylor, J.A., Iwamoto, G.A., Lubahn, D.B., Cooke, P.S., Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc. Natl. Acad. Sci. U. S. A. 97 (2000), 12729–12734.
100. Heneka, M.T., Landreth, G.E., PPARs in the brain. Biochim. Biophys. Acta 1771 (2007), 1031–1045.
101. Hering, H., Lin, C.C., Sheng, M., Lipid rafts in the maintenance of synapsesdendritic spines, and surface AMPA receptor stability. J. Neurosci. 23 (2003), 3262–3271.
102. Hertz, L., Dringen, R., Schousboe, A., Robinson, S.R., Astrocytes: glutamate producers for neurons. J. Neurosci. Res. 57 (1999), 417–428.
103. Hidalgo, J., Florit, S., Giralt, M., Ferrer, B., Keller, C., Pilegaard, H., Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat. Brain Behav. Immun. 24 (2010), 119–126.
104. Higuchi, S., Irie, K., Mishima, S., Araki, M., Ohji, M., Shirakawa, A., Akitake, Y., Matsuyama, K., Mishima, K., Mishima, K., Iwasaki, K., Fujiwara, M., The cannabinoid 1-receptor silent antagonist O-2050 attenuates preference for high-fat diet and activated astrocytes in mice. J. Pharmacol. Sci. 112 (2010), 369–372.
105. Higuchi, S., Irie, K., Yamaguchi, R., Katsuki, M., Araki, M., Ohji, M., Hayakawa, K., Mishima, S., Akitake, Y., Matsuyama, K., Mishima, K., Mishima, K., Iwasaki, K., Fujiwara, M., Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences. PLoS One, 7, 2012, e38609.
106. Hileman, S.M., Pierroz, D.D., Masuzaki, H., Bjorbaek, C., El-Haschimi, K., Banks, W.A., Flier, J.S., Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity. Endocrinology 143 (2002), 775–783.
107. Horvath, T.L., Gao, X.B., Input organization and plasticity of hypocretin neurons: possible clues to obesity's association with insomnia. Cell Metab. 1 (2005), 279–286.
108. Horvath, T.L., Naftolin, F., Kalra, S.P., Leranth, C., Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis. Endocrinology 131 (1992), 2461–2467.
109. Horvath, T.L., Sarman, B., Garcia-Caceres, C., Enriori, P.J., Sotonyi, P., Shanabrough, M., Borok, E., Argente, J., Chowen, J.A., Perez-Tilve, D., Pfluger, P.T., Bronneke, H.S., Levin, B.E., Diano, S., Cowley, M.A., Tschop, M.H., Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 14857–14880.
110. Hsuchou, H., He, Y., Kastin, A.J., Tu, H., Markadakis, E.N., Rogers, R.C., Fossier, P.B., Pan, W., Obesity induces functional astrocytic leptin receptors in hypothalamus. Brain 132 (2009), 889–902.
111. Hsuchou, H., Kastin, A.J., Tu, H., Joan Abbott, N., Couraud, P.O., Pan, W., Role of astrocytic leptin receptor subtypes on leptin permeation across hCMEC/D3 human brain endothelial cells. J. Neurochem. 115 (2010), 1288–1298.
112. Hsuchou, H., Pan, W., Barnes, M.J., Kastin, A.J., Leptin receptor mRNA in rat brain astrocytes. Peptides 30 (2009), 2275–2280.
113. Hursting, S.D., Dunlap, S.M., Obesity, metabolic dysregulation, and cancer: a growing concern and an inflammatory (and microenvironmental) issue. Ann. N. Y. Acad. Sci. 1271 (2012), 82–87.
114. Inyushkin, A.N., Bhumbra, G.S., Dyball, R.E., Leptin modulates spike coding in the rat suprachiasmatic nucleus. J. Neuroendocrinol. 21 (2009), 705–714.
115. Jayaram, B., Pan, W., Wang, Y., Hsuchou, H., Mace, A., Cornelissen-Guillaume, G.G., Mishra, P.K., Koza, R.A., Kastin, A.J., Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity. J. Appl. Physiol. 114 (2013), 734–741.
116. Joe, N., Scott, V., Brown, C.H., Glial regulation of extrasynaptic NMDA receptor-mediated excitation of supraoptic nucleus neurones during dehydration. J. Neuroendocrinol. 26 (2014), 35–42.
117. Jung-Testas, I., Baulieu, E.E., Steroid hormone receptors and steroid action in rat glial cells of the central and peripheral nervous system. J. Steroid Biochem. Mol. Biol. 65 (1998), 243–251.
118. Kacem, K., Lacombe, P., Seylaz, J., Bonvento, G., Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23 (1998), 1–10.
119. Kastin, A.J., Akerstrom, V., Glucose and insulin increase the transport of leptin through the blood-brain barrier in normal mice but not in streptozotocin-diabetic mice. Neuroendocrinology 73 (2001), 237–242.
120. Khakh, B.S., Sofroniew, M.V., Diversity of astrocyte functions and phenotypes in neural circuits. Nat. Neurosci. 18 (2015), 942–952.
121. Kim, J.D., Leyva, S., Diano, S., Hormonal regulation of the hypothalamic melanocortin system. Front. Physiol., 5, 2014, 480.
122. Kim, J.G., Suyama, S., Koch, M., Jin, S., Argente-Arizon, P., Argente, J., Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat. Neurosci. 17 (2014), 908–910.
123. Kiss, J., Csaba, Z., Csaki, A., Halasz, B., Glutamatergic innervation of neuropeptide Y and pro-opiomelanocortin-containing neurons in the hypothalamic arcuate nucleus of the rat. Eur. J. Neurosci. 21 (2005), 2111–2119.
124. Koch, M., Varela, L., Kim, J.G., Kim, J.D., Hernandez-Nuno, F., Simonds, S.E., Castorena, C.M., Vianna, C.R., Elmquist, J.K., Morozov, Y.M., Rakic, P., Bechmann, I., Cowley, M.A., Szigeti-Buck, K., Dietrich, M.O., Gao, X.B., Diano, S., Horvath, T.L., Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 519 (2015), 45–50.
125. Koga, S., Kojima, A., Ishikawa, C., Kuwabara, S., Arai, K., Yoshiyama, Y., Effects of diet-induced obesity and voluntary exercise in a tauopathy mouse model: implications of persistent hyperleptinemia and enhanced astrocytic leptin receptor expression. Neurobiol. Dis. 71 (2014), 180–192.
126. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., Kangawa, K., Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402 (1999), 656–660.
127. Krashes, M.J., Shah, B.P., Koda, S., Lowell, B.B., Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABANPY, and AgRP. Cell Metab. 18 (2013), 588–595.
128. Krude, H., Schnabel, D., Luck, W., Gruters, A., Implications of the phenotype of POMC deficiency for the role of POMC-derived peptides in skin physiology. Ann. N. Y. Acad. Sci. 885 (1999), 419–421.
129. Krul, E.S., Tang, J., Secretion of apolipoprotein E by an astrocytoma cell line. J. Neurosci. Res. 32 (1992), 227–238.
130. Lafrance, V., Inoue, W., Kan, B., Luheshi, G.N., Leptin modulates cell morphology and cytokine release in microglia. Brain Behav. Immun. 24 (2010), 358–365.
131. Lam, C.K., Chari, M., Lam, T.K., CNS regulation of glucose homeostasis. Physiology (Bethesda) 24 (2009), 159–170.
132. Lam, T.K.T., Gutierrez-Juarez, R., Pocai, A., Rossetti, L., Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309 (2005), 943–947.
133. Lam, T.K.T., Pocai, A., Gutierrez-Juarez, R., Obici, S., Bryan, J., Aguilar-Bryan, L., Schwartz, G.J., Rossetti, L., Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat. Med. 11 (2005), 320–327.
134. Lanfray, D., Arthaud, S., Ouellet, J., Compere, V., Do Rego, J.L., Leprince, J., Lefranc, B., Castel, H., Bouchard, C., Monge-Roffarello, B., Richard, D., Pelletier, G., Vaudry, H., Tonon, M.C., Morin, F., Gliotransmission and brain glucose sensing: critical role of endozepines. Diabetes 62 (2013), 801–810.
135. Larsen, R.S., Sjostrom, P.J., Synapse-type-specific plasticity in local circuits. Curr. Opin. Neurobiol. 35 (2015), 127–135.
136. Le Foll, C., Dunn-Meynell, A.A., Miziorko, H.M., Levin, B.E., Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 63 (2014), 1259–1269.
137. Le Foll, C., Dunn-Meynell, A.A., Miziorko, H.M., Levin, B.E., Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308 (2015), R872–R878.
138. Lee, G.H., Proenca, R., Montez, J.M., Carroll, K.M., Darvishzadeh, J.G., Lee, J.I., Friedman, J.M., Abnormal splicing of the leptin receptor in diabetic mice. Nature 379 (1996), 632–635.
139. Lee, K.M., MacLean, A.G., New advances on glial activation in health and disease. World J. Virol. 4 (2015), 42–55.
140. Lee, S.C., Liu, W., Dickson, D.W., Brosnan, C.F., Berman, J.W., Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J. Immunol. 150 (1993), 2659–2667.
141. Leloup, C., Allard, C., Carneiro, L., Fioramonti, X., Collins, S., Penicaud, L., Glucose and hypothalamic astrocytes: more than a fueling role?. Neuroscience, 2015.
142. Levian, C., Ruiz, E., Yang, X., The pathogenesis of obesity from a genomic and systems biology perspective. Yale J. Biol. Med. 87 (2014), 113–126.
143. Levin, B.E., Dunn-Meynell, A.A., Balkan, B., Keesey, R.E., Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am. J. Physiol. 273 (1997), R725–730.
144. Levin, B.E., Magnan, C., Dunn-Meynell, A., Foll, C.L., Metabolic sensing and the brain: who, what, where, and how?. Endocrinology 152 (2011), 2552–2557.
145. Levin, B.E., Magnan, C., Dunn-Meynell, A., Le Foll, C., Metabolic sensing and the brain: who, what, where, and how?. Endocrinology 152 (2011), 2552–2557.
146. Li, J., Tang, Y., Cai, D., IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nat. Cell Biol. 14 (2012), 999–1012.
147. Liu, T., Kong, D., Shah, B.P., Ye, C., Koda, S., Saunders, A., Ding, J.B., Yang, Z., Sabatini, B.L., Lowell, B.B., Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 73 (2012), 511–522.
148. Lobie, P.E., Garcia-Aragon, J., Lincoln, D.T., Barnard, R., Wilcox, J.N., Waters, M.J., Localization and ontogeny of growth hormone receptor gene expression in the central nervous system. Brain Res. Dev. Brain. Res. 74 (1993), 225–233.
149. Loos, R.J., The genetic epidemiology of melanocortin 4 receptor variants. Eur. J. Pharmacol. 660 (2011), 156–164.
150. Lopez, M., Tovar, S., Vazquez, M.J., Nogueiras, R., Senaris, R., Dieguez, C., Sensing the fat: fatty acid metabolism in the hypothalamus and the melanocortin system. Peptides 26 (2005), 1753–1758.
151. Ma, Y.J., Hill, D.F., Creswick, K.E., Costa, M.E., Cornea, A., Lioubin, M.N., Plowman, G.D., Ojeda, S.R., Neuregulins signaling via a glial erbB-2-erbB-4 receptor complex contribute to the neuroendocrine control of mammalian sexual development. J. Neurosci. 19 (1999), 9913–9927.
152. MacVicar, B.A., Newman, E.A., Astrocyte regulation of blood flow in the brain. Cold Spring Harb. Perspect. Biol., 2015, 7.
153. Malagon, M., Vaudry, H., Van Strien, F., Pelletier, G., Gracia-Navarro, F., Tonon, M.C., Ontogeny of diazepam-binding inhibitor-related peptides (endozepines) in the rat brain. Neuroscience 57 (1993), 777–786.
154. Malik, S., McGlone, F., Bedrossian, D., Dagher, A., Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 7 (2008), 400–409.
155. Martin-Rodriguez, E., Guillen-Grima, F., Marti, A., Brugos-Larumbe, A., Comorbidity associated with obesity in a large population: the APNA study. Obes. Res. Clin. Pract. 9:September–October (5) (2015), 435–447.
156. Marty, N., Dallaporta, M., Foretz, M., Emery, M., Tarussio, D., Bady, I., Binnert, C., Beermann, F., Thorens, B., Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors. J. Clin. Invest. 115 (2005), 3545–3553.
157. Marty, N., Dallaporta, M., Foretz, M., Emery, M., Tarussio, D., Bady, I., Binnert, C., Beermann, F., Thorens, B., Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors. J. Clin. Invest. 115 (2005), 3545–3553.
158. Marzban, F., Tweedle, C.D., Hatton, G.I., Reevaluation of the plasticity in the rat supraoptic nucleus after chronic dehydration using immunogold for oxytocin and vasopressin at the ultrastructural level. Brain Res. Bull. 28 (1992), 757–766.
159. McNay, D.E., Briancon, N., Kokoeva, M.V., Maratos-Flier, E., Flier, J.S., Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J. Clin. Invest. 122 (2012), 142–152.
160. Melcangi, R.C., Galbiati, M., Messi, E., Piva, F., Martini, L., Motta, M., Type 1 astrocytes influence luteinizing hormone-releasing hormone release from the hypothalamic cell line GT1-1: is transforming growth factor-beta the principle involved?. Endocrinology 136 (1995), 679–686.
161. Metna-Laurent, M., Marsicano, G., Rising stars: modulation of brain functions by astroglial type-1 cannabinoid receptors. Glia 63 (2015), 353–364.
162. Migrenne, S., Cruciani-Guglielmacci, C., Kang, L., Wang, R., Rouch, C., Lefèvre, A.-L., Ktorza, A., Routh, V.H., Levin, B.E., Magnan, C., Fatty acid signaling in the hypothalamus and the neural control of insulin secretion. Diabetes 55 (2006), S139–S144.
163. Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D.E., Tsukumo, D.M., Anhe, G., Amaral, M.E., Takahashi, H.K., Curi, R., Oliveira, H.C., Carvalheira, J.B., Bordin, S., Saad, M.J., Velloso, L.A., Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J. Neurosci. 29 (2009), 359–370.
164. Mizuno, T.M., Mobbs, C.V., Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 140 (1999), 814–817.
165. Montague, C.T., Farooqi, I.S., Whitehead, J.P., Soos, M.A., Rau, H., Wareham, N.J., Sewter, C.P., Digby, J.E., Mohammed, S.N., Hurst, J.A., Cheetham, C.H., Earley, A.R., Barnett, A.H., Prins, J.B., O'Rahilly, S., Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387 (1997), 903–908.
166. Moraes, J.C., Coope, A., Morari, J., Cintra, D.E., Roman, E.A., Pauli, J.R., Romanatto, T., Carvalheira, J.B., Oliveira, A.L., Saad, M.J., Velloso, L.A., High-fat diet induces apoptosis of hypothalamic neurons. PLoS One, 4, 2009, e5045.
167. Morgello, S., Uson, R.R., Schwartz, E.J., Haber, R.S., The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 14 (1995), 43–54.
168. Morselli, E., Frank, A.P., Palmer, B.F., Rodriguez-Navas, C., Criollo, A., Clegg, D.J., A sexually dimorphic hypothalamic response to chronic high-fat diet consumption. Int. J. Obes. (Lond.) 40:Feburary (2) (2016), 206–209.
169. Morselli, E., Fuente-Martin, E., Finan, B., Kim, M., Frank, A., Garcia-Caceres, C., Navas, C.R., Gordillo, R., Neinast, M., Kalainayakan, S.P., Li, D.L., Gao, Y., Yi, C.X., Hahner, L., Palmer, B.F., Tschop, M.H., Clegg, D.J., Hypothalamic PGC-1alpha protects against high-fat diet exposure by regulating ERalpha. Cell Rep. 9 (2014), 633–645.
170. Mounien, L., Marty, N., Tarussio, D., Metref, S., Genoux, D., Preitner, F., Foretz, M., Thorens, B., Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons. FASEB J. 24 (2010), 1747–1758.
171. Muller, T.D., Nogueiras, R., Andermann, M.L., Andrews, Z.B., Anker, S.D., Argente, J., Batterham, R.L., Benoit, S.C., Bowers, C.Y., Broglio, F., Casanueva, F.F., D'Alessio, D., Depoortere, I., Geliebter, A., Ghigo, E., Cole, P.A., Cowley, M., Cummings, D.E., Dagher, A., Diano, S., Dickson, S.L., Dieguez, C., Granata, R., Grill, H.J., Grove, K., Habegger, K.M., Heppner, K., Heiman, M.L., Holsen, L., Holst, B., Inui, A., Jansson, J.O., Kirchner, H., Korbonits, M., Laferrere, B., LeRoux, C.W., Lopez, M., Morin, S., Nakazato, M., Nass, R., Perez-Tilve, D., Pfluger, P.T., Schwartz, T.W., Seeley, R.J., Sleeman, M., Sun, Y., Sussel, L., Tong, J., Thorner, M.O., van der Lely, A.J., van der Ploeg, L.H., Zigman, J.M., Kojima, M., Kangawa, K., Smith, R.G., Horvath, T., Tschop, M.H., Ghrelin. Mol. Metab. 4 (2015), 437–460.
172. Murphy, B.A., Fakira, K.A., Song, Z., Beuve, A., Routh, V.H., AMP-activated protein kinase and nitric oxide regulate the glucose sensitivity of ventromedial hypothalamic glucose-inhibited neurons. Am. J. Physiol. Cell. Physiol. 297 (2009), C750–758.
173. Myers, M.G. Jr., Leibel, R.L., Seeley, R.J., Schwartz, M.W., Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol. Metab. 21 (2010), 643–651.
174. Naftolin, F., Mor, G., Horvath, T.L., Luquin, S., Fajer, A.B., Kohen, F., Garcia-Segura, L.M., Synaptic remodeling in the arcuate nucleus during the estrous cycle is induced by estrogen and precedes the preovulatory gonadotropin surge. Endocrinology 137 (1996), 5576–5580.
175. Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., Matsukura, S., A role for ghrelin in the central regulation of feeding. Nature 409 (2001), 194–198.
176. Narishima, R., Yamasaki, M., Hasegawa, S., Yoshida, S., Tanaka, S., Fukui, T., Leptin controls ketone body utilization in hypothalamic neuron. Neurosci. Lett. 490 (2011), 185–190.
177. Ojeda, S.R., The neurobiology of mammalian puberty: has the contribution of glial cells been underestimated?. J. NIH Res. 6 (1994), 51–56.
178. Ojeda, S.R., Lomniczi, A., Sandau, U.S., Glial-gonadotrophin hormone (GnRH) neurone interactions in the median eminence and the control of GnRH secretion. J. Neuroendocrinol. 20 (2008), 732–742.
179. Olmos, G., Naftolin, F., Perez, J., Tranque, P.A., Garcia-Segura, L.M., Synaptic remodeling in the rat arcuate nucleus during the estrous cycle. Neuroscience 32 (1989), 663–667.
180. Ollmann, M.M., Wilson, B.D., Yang, Y.K., Kerns, J.A., Chen, Y., Gantz, I., Barsh, G.S., Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278 (1997), 135–138.
181. Oomura, Y., Kimura, K., Ooyama, H., Maeno, T., Iki, M., Kuniyoshi, M., Reciprocal activities of the ventromedial and lateral hypothalamic areas of cats. Science 143 (1964), 484–485.
182. Oomura, Y., Ooyama, H., Sugimori, M., Nakamura, T., Yamada, Y., Glucose inhibition of the glucose-sensitive neurone in the rat lateral hypothalamus. Nature 247 (1974), 284–286.
183. Ottaway, N., Mahbod, P., Rivero, B., Norman, L.A., Gertler, A., D'Alessio, D.A., Perez-Tilve, D., Diet-induced obese mice retain endogenous leptin action. Cell Metab. 21 (2015), 877–882.
184. Palmer, B.F., Clegg, D.J., The sexual dimorphism of obesity. Mol. Cell Endocrinol. 402 (2015), 113–119.
185. Pan, W., Hsuchou, H., He, Y., Sakharkar, A., Cain, C., Yu, C., Kastin, A.J., Astrocyte leptin receptor (ObR) and leptin transport in adult-onset obese mice. Endocrinology 149 (2008), 2798–2806.
186. Pan, W., Hsuchou, H., Jayaram, B., Khan, R.S., Huang, E.Y., Wu, X., Chen, C., Kastin, A.J., Leptin action on nonneuronal cells in the CNS: potential clinical applications. Ann. N. Y. Acad. Sci. 1264 (2012), 64–71.
187. Pan, W., Hsuchou, H., Xu, C., Wu, X., Bouret, S.G., Kastin, A.J., Astrocytes modulate distribution and neuronal signaling of leptin in the hypothalamus of obese A vy mice. J. Mol. Neurosci. 43 (2011), 478–484.
188. Panov, A., Orynbayeva, Z., Vavilin, V., Lyakhovich, V., Fatty acids in energy metabolism of the central nervous system. BioMed. Res. Int., 2014, 2014, 472459.
189. Parkash, J., Messina, A., Langlet, F., Cimino, I., Loyens, A., Mazur, D., Gallet, S., Balland, E., Malone, S.A., Pralong, F., Cagnoni, G., Schellino, R., De Marchis, S., Mazzone, M., Pasterkamp, R.J., Tamagnone, L., Prevot, V., Giacobini, P., Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence. Nat. Commun., 6, 2015, 6385.
190. Parpura, V., Basarsky, T.A., Liu, F., Jeftinija, K., Jeftinija, S., Haydon, P.G., Glutamate-mediated astrocyte-neuron signalling. Nature 369 (1994), 744–747.
191. Pellerin, L., Magistretti, P.J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U. S. A. 91 (1994), 10625–10629.
192. Perea, G., Navarrete, M., Araque, A., Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 32 (2009), 421–431.
193. Perlmutter, L.S., Hatton, G.I., Tweedle, C.D., Plasticity in the in vitro neurohypophysis: effects of osmotic changes on pituicytes. Neuroscience 12 (1984), 503–511.
194. Perlmutter, L.S., Tweedle, C.D., Hatton, G.I., Neuronal/glial plasticity in the supraoptic dendritic zone: dendritic bundling and double synapse formation at parturition. Neuroscience 13 (1984), 769–779.
195. Perlmutter, L.S., Tweedle, C.D., Hatton, G.I., Neuronal/glial plasticity in the supraoptic dendritic zone in response to acute and chronic dehydration. Brain Res. 361 (1985), 225–232.
196. Pfrieger, F.W., Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes?. Bioessays 25 (2003), 72–78.
197. Pinto, S., Roseberry, A.G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J.M., Horvath, T.L., Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304 (2004), 110–115.
198. Prevot, V., Croix, D., Bouret, S., Dutoit, S., Tramu, G., Stefano, G.B., Beauvillain, J.C., Definitive evidence for the existence of morphological plasticity in the external zone of the median eminence during the rat estrous cycle: implication of neuro-glio-endothelial interactions in gonadotropin-releasing hormone release. Neuroscience 94 (1999), 809–819.
199. Prevot, V., Dehouck, B., Poulain, P., Beauvillain, J.C., Buee-Scherrer, V., Bouret, S., Neuronal-glial-endothelial interactions and cell plasticity in the postnatal hypothalamus: implications for the neuroendocrine control of reproduction. Psychoneuroendocrinology 32:suppl. 1 (2007), S46–51.
200. Prosser, R.A., Edgar, D.M., Heller, H.C., Miller, J.D., A possible glial role in the mammalian circadian clock. Brain Res. 643 (1994), 296–301.
201. Rage, F., Lee, B.J., Ma, Y.J., Ojeda, S.R., Estradiol enhances prostaglandin E2 receptor gene expression in luteinizing hormone-releasing hormone (LHRH) neurons and facilitates the LHRH response to PGE2 by activating a glia-to-neuron signaling pathway. J. Neurosci. 17 (1997), 9145–9156.
202. Reis, W.L., Yi, C.X., Gao, Y., Tschop, M.H., Stern, J.E., Brain innate immunity regulates hypothalamic arcuate neuronal activity and feeding behavior. Endocrinology 156 (2015), 1303–1315.
203. Robertson, C.L., Srivastava, J., Siddiq, A., Gredler, R., Emdad, L., Rajasekaran, D., Akiel, M., Shen, X.N., Corwin, F., Sundaresan, G., Zweit, J., Croniger, C., Gao, X., Ghosh, S., Hylemon, P.B., Subler, M.A., Windle, J.J., Fisher, P.B., Sarkar, D., Astrocyte elevated gene-1 (AEG-1) regulates lipid homeostasis. J. Biol. Chem. 290 (2015), 18227–18236.
204. Rodriguez, E.M., Blazquez, J.L., Pastor, F.E., Pelaez, B., Pena, P., Peruzzo, B., Amat, P., Hypothalamic tanycytes: a key component of brain-endocrine interaction. Int. Rev. Cytol. 247 (2005), 89–164.
205. Ross, M.G., Desai, M., Developmental programming of offspring obesity, adipogenesis, and appetite. Clin. Obstet. Gynecol. 56 (2013), 529–536.
206. Rouach, N., Koulakoff, A., Abudara, V., Willecke, K., Giaume, C., Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322 (2008), 1551–1555.
207. Sandau, U.S., Mungenast, A.E., Alderman, Z., Sardi, S.P., Fogel, A.I., Taylor, B., Parent, A.S., Biederer, T., Corfas, G., Ojeda, S.R., SynCAM1a synaptic adhesion molecule, is expressed in astrocytes and contributes to erbB4 receptor-mediated control of female sexual development. Endocrinology 152 (2011), 2364–2376.
208. Sandau, U.S., Mungenast, A.E., McCarthy, J., Biederer, T., Corfas, G., Ojeda, S.R., The synaptic cell adhesion moleculeSynCAM1, mediates astrocyte-to-astrocyte and astrocyte-to-GnRH neuron adhesiveness in the mouse hypothalamus. Endocrinology 152 (2011), 2353–2363.
209. Schneeberger, M., Gomis, R., Claret, M., Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J. Endocrinol. 220 (2014), T25–46.
210. Schousboe, A., Bak, L.K., Sickmann, H.M., Sonnewald, U., Waagepetersen, H.S., Energy substrates to support glutamatergic and GABAergic synaptic function: role of glycogen glucose and lactate. Neurotox. Res. 12 (2007), 263–268.
211. Schwartz, M.W., Seeley, R.J., Campfield, L.A., Burn, P., Baskin, D.G., Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest. 98 (1996), 1101–1106.
212. Secher, A., Jelsing, J., Baquero, A.F., Hecksher-Sorensen, J., Cowley, M.A., Dalboge, L.S., Hansen, G., Grove, K.L., Pyke, C., Raun, K., Schaffer, L., Tang-Christensen, M., Verma, S., Witgen, B.M., Vrang, N., Bjerre Knudsen, L., The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J. Clin. Invest. 124 (2014), 4473–4488.
213. Serrano, A., Haddjeri, N., Lacaille, J.C., Robitaille, R., GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression. J. Neurosci. 26 (2006), 5370–5382.
214. Shen, L., Tso, P., Wang, D.Q.H., Woods, S.C., Davidson, W.S., Sakai, R., Liu, M., Up-regulation of apolipoprotein E by leptin in the hypothalamus of mice and rats. Physiol. Behav. 98 (2009), 223–228.
215. Shen, L., Tso, P., Woods, S.C., Clegg, D.J., Barber, K.L., Carey, K., Liu, M., Brain apolipoprotein E: an important regulator of food intake in rats. Diabetes 57 (2008), 2092–2098.
216. Song, Z., Levin, B.E., McArdle, J.J., Bakhos, N., Routh, V.H., Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 50 (2001), 2673–2681.
217. Spence, R.D., Hamby, M.E., Umeda, E., Itoh, N., Du, S., Wisdom, A.J., Cao, Y., Bondar, G., Lam, J., Ao, Y., Sandoval, F., Suriany, S., Sofroniew, M.V., Voskuhl, R.R., Neuroprotection mediated through estrogen receptor-alpha in astrocytes. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 8867–8872.
218. Srivastava, J., Robertson, C.L., Rajasekaran, D., Gredler, R., Siddiq, A., Emdad, L., Mukhopadhyay, N.D., Ghosh, S., Hylemon, P.B., Gil, G., Shah, K., Bhere, D., Subler, M.A., Windle, J.J., Fisher, P.B., Sarkar, D., AEG-1 regulates retinoid X receptor and inhibits retinoid signaling. Cancer Res. 74 (2014), 4364–4377.
219. Stanley, B.G., Urstadt, K.R., Charles, J.R., Kee, T., Glutamate and GABA in lateral hypothalamic mechanisms controlling food intake. Physiol. Behav. 104 (2011), 40–46.
220. Stella, N., Cannabinoid signaling in glial cells. Glia 48 (2004), 267–277.
221. Sternson, S.M., Shepherd, G.M., Friedman, J.M., Topographic mapping of VMH −> arcuate nucleus microcircuits and their reorganization by fasting. Nat. Neurosci. 8 (2005), 1356–1363.
222. Stolarczyk, E., Guissard, C., Michau, A., Even, P.C., Grosfeld, A., Serradas, P., Lorsignol, A., Penicaud, L., Brot-Laroche, E., Leturque, A., Le Gall, M., Detection of extracellular glucose by GLUT2 contributes to hypothalamic control of food intake. Am. J. Physiol. Endocrinol. Metab. 298 (2010), E1078–1087.
223. Stucchi, P., Gil-Ortega, M., Merino, B., Guzman-Ruiz, R., Cano, V., Valladolid-Acebes, I., Somoza, B., Le Gonidec, S., Argente, J., Valet, P., Chowen, J.A., Fernandez-Alfonso, M., Ruiz-Gayo, M., Circadian feeding drive of metabolic activity in adipose tissue and not hyperphagia triggers overweight in mice: is there a role of the pentose-phosphate pathway?. Endocrinology 153 (2012), 690–699.
224. Suzuki, R., Lee, K., Jing, E., Biddinger, S.B., McDonald, J.G., Montine, T.J., Craft, S., Kahn, C.R., Diabetes and insulin in regulation of brain cholesterol metabolism. Cell Metab. 12 (2010), 567–579.
225. Taib, B., Bouyakdan, K., Hryhorczuk, C., Rodaros, D., Fulton, S., Alquier, T., Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes. J. Biol. Chem. 288 (2013), 37216–37229.
226. Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K.J., Smutko, J.S., Mays, G.G., Wool, E.A., Monroe, C.A., Tepper, R.I., Identification and expression cloning of a leptin receptor, OB-R. Cell 83 (1995), 1263–1271.
227. Tcherepanova, I., Puigserver, P., Norris, J.D., Spiegelman, B.M., McDonnell, D.P., Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1. J. Biol. Chem. 275 (2000), 16302–16308.
228. Thaler, J.P., Yi, C.X., Schur, E.A., Guyenet, S.J., Hwang, B.H., Dietrich, M.O., Zhao, X., Sarruf, D.A., Izgur, V., Maravilla, K.R., Nguyen, H.T., Fischer, J.D., Matsen, M.E., Wisse, B.E., Morton, G.J., Horvath, T.L., Baskin, D.G., Tschop, M.H., Schwartz, M.W., Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Invest. 122 (2012), 153–162.
229. Theodosis, D.T., Montagnese, C., Rodriguez, F., Vincent, J.D., Poulain, D.A., Oxytocin induces morphological plasticity in the adult hypothalamo-neurohypophysial system. Nature 322 (1986), 738–740.
230. Theodosis, D.T., Paut, L., Tappaz, M.L., Immunocytochemical analysis of the GABAergic innervation of oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus. Neuroscience 19 (1986), 207–222.
231. Theodosis, D.T., Piet, R., Poulain, D.A., Oliet, S.H., Neuronal:glial and synaptic remodeling in the adult hypothalamus: functional consequences and role of cell surface and extracellular matrix adhesion molecules. Neurochem. Int. 45 (2004), 491–501.
232. Theodosis, D.T., Poulain, D.A., Evidence for structural plasticity in the supraoptic nucleus of the rat hypothalamus in relation to gestation and lactation. Neuroscience 11 (1984), 183–193.
233. Theodosis, D.T., Poulain, D.A., Evidence that oxytocin-secreting neurones are involved in the ultrastructural reorganisation of the rat supraoptic nucleus apparent at lactation. Cell Tissue Res. 235 (1984), 217–219.
234. Thorens, B., Guillam, M.T., Beermann, F., Burcelin, R., Jaquet, M., Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion. J. Biol. Chem. 275 (2000), 23751–23758.
235. Tschöp, M., Smiley, D.L., Heiman, M.L., Ghrelin induces adiposity in rodents. Nature 407 (2000), 908–913.
236. Tsukumo, D.M., Carvalho-Filho, M.A., Carvalheira, J.B., Prada, P.O., Hirabara, S.M., Schenka, A.A., Araujo, E.P., Vassallo, J., Curi, R., Velloso, L.A., Saad, M.J., Loss-of-function mutation in toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56 (2007), 1986–1998.
237. Tweedle, C.D., Hatton, G.I., Ultrastructural changes in rat hypothalamic neurosecretory cells and their associated glia during minimal dehydration and rehydration. Cell Tissue Res. 181 (1977), 59–72.
238. Valdearcos, M., Xu, A.W., Koliwad, S.K., Hypothalamic inflammation in the control of metabolic function. Annu. Rev. Physiol. 77 (2015), 131–160.
239. Vannucci, S.J., Maher, F., Simpson, I.A., Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia 21 (1997), 2–21.
240. Vartak-Sharma, N., Gelman, B.B., Joshi, C., Borgamann, K., Ghorpade, A., Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-kappaB signaling and excitatory amino acid transporter-2 repression. J. Biol. Chem. 289 (2014), 19599–19612.
241. Vimr, E.R., McCoy, R.D., Vollger, H.F., Wilkison, N.C., Troy, F.A., Use of prokaryotic-derived probes to identify poly(sialic acid) in neonatal neuronal membranes. Proc. Natl. Acad. Sci. U. S. A. 81 (1984), 1971–1975.
242. Wabitsch, M., Funcke, J.B., Lennerz, B., Kuhnle-Krahl, U., Lahr, G., Debatin, K.M., Vatter, P., Gierschik, P., Moepps, B., Fischer-Posovszky, P., Biologically inactive leptin and early-onset extreme obesity. N. Engl. J. Med. 372 (2015), 48–54.
243. Wallenius, K., Wallenius, V., Sunter, D., Dickson, S.L., Jansson, J.-O., Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem. Biophys. Res. Commun. 293 (2002), 560–565.
244. Wallenius, V., Wallenius, K., Ahren, B., Rudling, M., Carlsten, H., Dickson, S.L., Ohlsson, C., Jansson, J.O., Interleukin-6-deficient mice develop mature-onset obesity. Nat. Med. 8 (2002), 75–79.
245. Wang, Y.F., Hatton, G.I., Interaction of extracellular signal-regulated protein kinase 1/2 with actin cytoskeleton in supraoptic oxytocin neurons and astrocytes: role in burst firing. J. Neurosci. 27 (2007), 13822–13834.
246. Wang, Y.F., Hatton, G.I., Astrocytic plasticity and patterned oxytocin neuronal activity: dynamic interactions. J. Neurosci. 29 (2009), 1743–1754.
247. Wauman, J., Tavernier, J., Leptin receptor signaling: pathways to leptin resistance. Front. Biosci. (Landmark Ed.) 16 (2011), 2771–2793.
248. Webber, E.S., Bonci, A., Krashes, M.J., The elegance of energy balance: Insight from circuit-level manipulations. Synapse 69 (2015), 461–474.
249. Willesen, M.G., Kristensen, P., Romer, J., Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology 70 (1999), 306–316.
250. Witkin, J.W., Ferin, M., Popilskis, S.J., Silverman, A.J., Effects of gonadal steroids on the ultrastructure of GnRH neurons in the rhesus monkey: synaptic input and glial apposition. Endocrinology 129 (1991), 1083–1092.
251. Xue, B., Kahn, B.B., AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J. Physiol. 574 (2006), 73–83.
252. Yang, L., Qi, Y., Yang, Y., Astrocytes control food intake by inhibiting AGRP neuron activity via adenosine A1 receptors. Cell Rep. 11 (2015), 798–807.
253. Yang, Y., Atasoy, D., Su, H.H., Sternson, S.M., Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell 146 (2011), 992–1003.
254. Young, J.K., Baker, J.H., Montes, M.I., The brain response to 2-deoxy glucose is blocked by a glial drug. Pharmacol. Biochem. Behav. 67 (2000), 233–239.
255. Zhao, J., Fu, Y., Liu, C.C., Shinohara, M., Nielsen, H.M., Dong, Q., Kanekiyo, T., Bu, G., Retinoic acid isomers facilitate apolipoprotein E production and lipidation in astrocytes through the retinoid X receptor/retinoic acid receptor pathway. J. Biol. Chem. 289 (2014), 11282–11292.