Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis

Abstract

Communication between the periphery and the brain is key for maintaining energy homeostasis. To do so, peripheral signals from the circulation reach the brain via the circumventricular organs (CVOs), which are characterized by fenestrated vessels lacking the protective blood–brain barrier (BBB). Glial cells, by virtue of their plasticity and their ideal location at the interface of blood vessels and neurons, participate in the integration and transmission of peripheral information to neuronal networks in the brain for the neuroendocrine control of whole-body metabolism. Metabolic diseases, such as obesity and type 2 diabetes, can disrupt the brain-to-periphery communication mediated by glial cells, highlighting the relevance of these cell types in the pathophysiology of such complications. An improved understanding of how glial cells integrate and respond to metabolic and humoral signals has become a priority for the discovery of promising therapeutic strategies to treat metabolic disorders. This Review highlights the role of glial cells in the exchange of metabolic signals between the periphery and the brain that are relevant for the regulation of whole-body energy homeostasis.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: The cross-talk between the brain and the peripheral organs via metabolic signals for energy homeostasis.
Fig. 2: Leptin and other circulating signals are transported from the periphery to hypothalamic areas around the 3V by tanycytes.
Fig. 3: Microglia in HFD-induced obesity and IL-1β/LPS-induced activation.

References

  1. Garcia-Caceres, C. et al. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nat. Neurosci. 22, 7–14 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. Chowen, J. A., Frago, L. M. & Fernandez-Alfonso, M. S. Physiological and pathophysiological roles of hypothalamic astrocytes in metabolism. J. Neuroendocrinol. 31, e12671 (2019).

    Article  PubMed  CAS  Google Scholar 

  3. Clasadonte, J. & Prevot, V. The special relationship: glia–neuron interactions in the neuroendocrine hypothalamus. Nat. Rev. Endocrinol. 14, 25–44 (2018).

    Article  CAS  PubMed  Google Scholar 

  4. Al Massadi, O., Lopez, M., Tschop, M., Dieguez, C. & Nogueiras, R. Current understanding of the hypothalamic ghrelin pathways inducing appetite and adiposity. Trends Neurosci. 40, 167–180 (2017).

    Article  CAS  PubMed  Google Scholar 

  5. Friedman, J. M. Leptin and the endocrine control of energy balance. Nat. Metab. 1, 754–764 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Campbell, J. E. & Newgard, C. B. Mechanisms controlling pancreatic islet cell function in insulin secretion. Nat. Rev. Mol. Cell Biol. 22, 142–158 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Prevot, V. et al. The versatile tanycyte: a hypothalamic integrator of reproduction and energy metabolism. Endocr. Rev. 39, 333–368 (2018).

    Article  PubMed  Google Scholar 

  8. Yeo, G. S. & Heisler, L. K. Unraveling the brain regulation of appetite: lessons from genetics. Nat. Neurosci. 15, 1343–1349 (2012).

    Article  CAS  PubMed  Google Scholar 

  9. Cone, R. D. Anatomy and regulation of the central melanocortin system. Nat. Neurosci. 8, 571–578 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Dubern, B. et al. Mutational analysis of the pro-opiomelanocortin gene in French obese children led to the identification of a novel deleterious heterozygous mutation located in the α-melanocyte stimulating hormone domain. Pediatr. Res. 63, 211–216 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Chowen, J. A. et al. The role of astrocytes in the hypothalamic response and adaptation to metabolic signals. Prog. Neurobiol. 144, 68–87 (2016).

    Article  PubMed  Google Scholar 

  12. Kim, J. G. et al. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat. Neurosci. 17, 908–910 (2014).

    Article  CAS  PubMed  Google Scholar 

  13. Varela, L. et al. Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice. J. Clin. Invest. 131, e144239 (2021).

    Article  CAS  PubMed Central  Google Scholar 

  14. Garcia-Caceres, C. et al. Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166, 867–880 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gao, Y. et al. Disruption of lipid uptake in astroglia exacerbates diet-induced obesity. Diabetes 66, 2555–2563 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Varela, L. et al. Astrocytic lipid metabolism determines susceptibility to diet-induced obesity. Sci. Adv. 7, eabj2814 (2021).

    Article  CAS  PubMed  Google Scholar 

  17. Kreft, M., Bak, L. K., Waagepetersen, H. S. & Schousboe, A. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation. ASN Neuro 4, e00086 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Bonvento, G. & Bolanos, J. P. Astrocyte–neuron metabolic cooperation shapes brain activity. Cell Metab. 33, 1546–1564 (2021).

    Article  CAS  PubMed  Google Scholar 

  19. Obradovic, M. et al. Leptin and obesity: role and clinical implication. Front Endocrinol. 12, 585887 (2021).

    Article  Google Scholar 

  20. Glaum, S. R. et al. Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus. Mol. Pharmacol. 50, 230–235 (1996).

    CAS  PubMed  Google Scholar 

  21. Garcia-Caceres, C. et al. Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels. Endocrinology 152, 1809–1818 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fuente-Martin, E. et al. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J. Clin. Invest. 122, 3900–3913 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Banks, W. A. The blood–brain barrier as an endocrine tissue. Nat. Rev. Endocrinol. 15, 444–455 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Duquenne, M. et al. Leptin brain entry via a tanycytic LepR–EGFR shuttle controls lipid metabolism and pancreas function. Nat. Metab. 3, 1071–1090 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Balland, E. et al. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab. 19, 293–301 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Butiaeva, L. I. et al. Leptin receptor-expressing pericytes mediate access of hypothalamic feeding centers to circulating leptin. Cell Metab. 33, 1433–1448 (2021).

    Article  CAS  PubMed  Google Scholar 

  27. Djogo, T. et al. Adult NG2–glia are required for median eminence-mediated leptin sensing and body weight control. Cell Metab. 23, 797–810 (2016).

    Article  CAS  PubMed  Google Scholar 

  28. Muller, T. D. et al. Ghrelin. Mol. Metab. 4, 437–460 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen, N. et al. Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding. eLife 5, e18716 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Clasadonte, J. et al. Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation. Proc. Natl Acad. Sci. USA 108, 16104–16109 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lebrun, B. et al. Glial endozepines and energy balance: old peptides with new tricks. Glia 69, 1079–1093 (2021).

    Article  CAS  PubMed  Google Scholar 

  32. Bouyakdan, K. et al. The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system. J. Clin. Invest. 129, 2417–2430 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Pellerin, L. & Magistretti, P. J. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl Acad. Sci. USA 91, 10625–10629 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bergersen, L. H. Lactate transport and signaling in the brain: potential therapeutic targets and roles in body–brain interaction. J. Cereb. Blood Flow. Metab. 35, 176–185 (2015).

    Article  CAS  PubMed  Google Scholar 

  35. Rafiki, A., Boulland, J. L., Halestrap, A. P., Ottersen, O. P. & Bergersen, L. Highly differential expression of the monocarboxylate transporters MCT2 and MCT4 in the developing rat brain. Neuroscience 122, 677–688 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Lhomme, T. et al. Tanycytic networks mediate energy balance by feeding lactate to glucose-insensitive POMC neurons. J. Clin. Invest. 131, e140521 (2021).

    Article  PubMed Central  Google Scholar 

  37. Ordenes, P. et al. Lactate activates hypothalamic POMC neurons by intercellular signaling. Sci. Rep. 11, 21644 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tirou, L. et al. Sonic Hedgehog receptor Patched deficiency in astrocytes enhances glucose metabolism in mice. Mol. Metab. 47, 101172 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nuzzaci, D. et al. Postprandial hyperglycemia stimulates neuroglial plasticity in hypothalamic POMC neurons after a balanced meal. Cell Rep. 30, 3067–3078 (2020).

    Article  CAS  PubMed  Google Scholar 

  40. Scharbarg, E. et al. Astrocyte-derived adenosine is central to the hypnogenic effect of glucose. Sci. Rep. 6, 19107 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Benani, A. et al. Food intake adaptation to dietary fat involves PSA-dependent rewiring of the arcuate melanocortin system in mice. J. Neurosci. 32, 11970–11979 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Allard, C. et al. Hypothalamic astroglial connexins are required for brain glucose sensing-induced insulin secretion. J. Cereb. Blood Flow. Metab. 34, 339–346 (2014).

    Article  CAS  PubMed  Google Scholar 

  43. Giaume, C., Leybaert, L., Naus, C. C. & Saez, J. C. Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles. Front. Pharm. 4, 88 (2013).

    Article  CAS  Google Scholar 

  44. Cheung, G., Chever, O. & Rouach, N. Connexons and pannexons: newcomers in neurophysiology. Front. Cell Neurosci. 8, 348 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Clasadonte, J., Scemes, E., Wang, Z., Boison, D. & Haydon, P. G. Connexin 43-mediated astroglial metabolic networks contribute to the regulation of the sleep–wake cycle. Neuron 95, 1365–1380 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fioramonti, X. et al. Characterization of glucosensing neuron subpopulations in the arcuate nucleus: integration in neuropeptide Y and pro-opio melanocortin networks? Diabetes 56, 1219–1227 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. 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, 2673–2681 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Claret, M. et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J. Clin. Invest. 117, 2325–2336 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Thaler, J. P. et al. Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Invest. 122, 153–162 (2012).

    Article  CAS  PubMed  Google Scholar 

  50. Douglass, J. D., Dorfman, M. D., Fasnacht, R., Shaffer, L. D. & Thaler, J. P. Astrocyte IKKβ/NF-κB signaling is required for diet-induced obesity and hypothalamic inflammation. Mol. Metab. 6, 366–373 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cai, D. & Khor, S. Hypothalamic microinflammation. Handb. Clin. Neurol. 181, 311–322 (2021).

    Article  PubMed  Google Scholar 

  52. Zhang, X. et al. Hypothalamic IKKβ/NF-κB and ER stress link overnutrition to energy imbalance and obesity. Cell 135, 61–73 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kleinridders, A. et al. MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab. 10, 249–259 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Benzler, J. et al. Central inhibition of IKKβ/NF-κB signaling attenuates high-fat diet-induced obesity and glucose intolerance. Diabetes 64, 2015–2027 (2015).

    Article  CAS  PubMed  Google Scholar 

  55. Zhang, Y., Reichel, J. M., Han, C., Zuniga-Hertz, J. P. & Cai, D. Astrocytic process plasticity and IKKβ/NF-κB in central control of blood glucose, blood pressure, and body weight. Cell Metab. 25, 1091–1102 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rahman, M. H. et al. Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes. Nat. Commun. 11, 5906 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Campbell, J. N. et al. A molecular census of arcuate hypothalamus and median eminence cell types. Nat. Neurosci. 20, 484–496 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Prevot, V., Nogueiras, R. & Schwaninger, M. Tanycytes in the infundibular nucleus and median eminence and their role in the blood–brain barrier. Handb. Clin. Neurol. 180, 253–273 (2021).

    Article  PubMed  Google Scholar 

  59. Nampoothiri, S., Duquenne, M. & Prevot, V. in Glial-Neuronal Signaling in Neuroendocrine Systems, Vol. 11 (eds. Tasker, J. G., Bains, J. S. & Chowen, J. A.) 255–284 (Springer Cham, 2021).

  60. Lee, D. A. et al. Dietary and sex-specific factors regulate hypothalamic neurogenesis in young adult mice. Front. Neurosci. 8, 157 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sharif, A., Fitzsimons, C. P. & Lucassen, P. J. Neurogenesis in the adult hypothalamus: a distinct form of structural plasticity involved in metabolic and circadian regulation, with potential relevance for human pathophysiology. Handb. Clin. Neurol. 179, 125–140 (2021).

    Article  PubMed  Google Scholar 

  62. Haan, N. et al. Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J. Neurosci. 33, 6170–6180 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Langlet, F. et al. Tanycytic VEGF-A boosts blood–hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab. 17, 607–617 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mullier, A., Bouret, S. G., Prevot, V. & Dehouck, B. Differential distribution of tight junction proteins suggests a role for tanycytes in blood–hypothalamus barrier regulation in the adult mouse brain. J. Comp. Neurol. 518, 943–962 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Schaeffer, M. et al. Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons. Proc. Natl Acad. Sci. USA 110, 1512–1517 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jiang, H. et al. MCH neurons regulate permeability of the median eminence barrier. Neuron 107, 306–319 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Caron, E., Sachot, C., Prevot, V. & Bouret, S. G. Distribution of leptin-sensitive cells in the postnatal and adult mouse brain. J. Comp. Neurol. 518, 459–476 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Caro, J. F. et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348, 159–161 (1996).

    Article  CAS  PubMed  Google Scholar 

  69. Schwartz, M. W., Peskind, E., Raskind, M., Boyko, E. J. & Porte, D. Jr. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat. Med. 2, 589–593 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Chmielewski, A. et al. Preclinical assessment of leptin transport into the cerebrospinal fluid in diet-induced obese minipigs. Obesity 27, 950–956 (2019).

    Article  CAS  PubMed  Google Scholar 

  71. Frederich, R. C. et al. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat. Med. 1, 1311–1314 (1995).

    Article  CAS  PubMed  Google Scholar 

  72. Hummel, K. P., Dickie, M. M. & Coleman, D. L. Diabetes, a new mutation in the mouse. Science 153, 1127–1128 (1966).

    Article  CAS  PubMed  Google Scholar 

  73. Wyse, B. M. & Dulin, W. E. The influence of age and dietary conditions on diabetes in the db mouse. Diabetologia 6, 268–273 (1970).

    Article  CAS  PubMed  Google Scholar 

  74. Lee, G. H. et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 379, 632–635 (1996).

    Article  CAS  PubMed  Google Scholar 

  75. Guillebaud, F. et al. Glial endozepines reverse high-fat diet-induced obesity by enhancing hypothalamic response to peripheral leptin. Mol. Neurobiol. 57, 3307–3333 (2020).

    Article  CAS  PubMed  Google Scholar 

  76. Yoo, S., Cha, D., Kim, D. W., Hoang, T. V. & Blackshaw, S. Tanycyte-independent control of hypothalamic leptin signaling. Front. Neurosci. 13, 240 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Porniece Kumar, M. et al. Insulin signalling in tanycytes gates hypothalamic insulin uptake and regulation of AgRP neuron activity. Nat. Metab. 3, 1662–1679 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Collden, G. et al. Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin. Mol. Metab. 4, 15–24 (2015).

    Article  CAS  PubMed  Google Scholar 

  79. Uriarte, M. et al. Circulating ghrelin crosses the blood–cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms. Mol. Cell. Endocrinol. 538, 111449 (2021).

    Article  CAS  PubMed  Google Scholar 

  80. Liang, Q. et al. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting. Diabetes 63, 4064–4075 (2014).

    Article  CAS  PubMed  Google Scholar 

  81. Owen, B. M. et al. FGF21 contributes to neuroendocrine control of female reproduction. Nat. Med. 19, 1153–1156 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Xu, C. et al. KLB, encoding β-Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism. EMBO Mol. Med. 9, 1379–1397 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pena-León, V. et al. Prolonged breastfeeding protects from obesity by hypothalamic action of hepatic FGF21. Nat. Metab. (in the press).

  84. Kaminskas, B. et al. Characterisation of endogenous players in fibroblast growth factor-regulated functions of hypothalamic tanycytes and energy-balance nuclei. J. Neuroendocrinol. 31, e12750 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Bottcher, M. et al. NF-κB signaling in tanycytes mediates inflammation-induced anorexia. Mol. Metab. 39, 101022 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Frayling, C., Britton, R. & Dale, N. ATP-mediated glucosensing by hypothalamic tanycytes. J. Physiol. 589, 2275–2286 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lazutkaite, G., Solda, A., Lossow, K., Meyerhof, W. & Dale, N. Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Mol. Metab. 6, 1480–1492 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hofmann, K. et al. Tanycytes and a differential fatty acid metabolism in the hypothalamus. Glia 65, 231–249 (2017).

    Article  PubMed  Google Scholar 

  89. Geller, S. et al. Tanycytes regulate lipid homeostasis by sensing free fatty acids and signaling to key hypothalamic neuronal populations via FGF21 secretion. Cell Metab. 30, 833–844 e837 (2019).

    Article  CAS  PubMed  Google Scholar 

  90. Benford, H. et al. A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes. Glia 65, 773–789 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Sanders, N. M., Dunn-Meynell, A. A. & Levin, B. E. Third ventricular alloxan reversibly impairs glucose counterregulatory responses. Diabetes 53, 1230–1236 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Haddad-Tovolli, R. & Claret, M. Cooperative tanycytes fuel the neuronal tank. J. Clin. Invest. 131, e153279 (2021).

    Article  CAS  Google Scholar 

  93. Bolborea, M., Pollatzek, E., Benford, H., Sotelo-Hitschfeld, T. & Dale, N. Hypothalamic tanycytes generate acute hyperphagia through activation of the arcuate neuronal network. Proc. Natl Acad. Sci. USA 117, 14473–14481 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Cortes-Campos, C. et al. MCT expression and lactate influx/efflux in tanycytes involved in glia–neuron metabolic interaction. PLoS ONE 6, e16411 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Conductier, G. et al. Melanin-concentrating hormone regulates beat frequency of ependymal cilia and ventricular volume. Nat. Neurosci. 16, 845–847 (2013).

    Article  CAS  PubMed  Google Scholar 

  96. Rodriguez-Cortes, B. et al. Suprachiasmatic nucleus-mediated glucose entry into the arcuate nucleus determines the daily rhythm in blood glycemia. Curr. Biol. 32, 796–805 (2022).

    Article  CAS  PubMed  Google Scholar 

  97. Imbernon, M., Dehouck, B. & Prevot, V. Glycemic control: tanycytes march to the beat of the suprachiasmatic drummer. Curr. Biol. 32, R173–R176 (2022).

    Article  CAS  PubMed  Google Scholar 

  98. Marcelin, G. et al. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism. Mol. Metab. 3, 19–28 (2014).

    Article  CAS  PubMed  Google Scholar 

  99. Brown, J. M. et al. Role of hypothalamic MAPK/ERK signaling and central action of FGF1 in diabetes remission. iScience 24, 102944 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bentsen, M. A. et al. Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. Nat. Commun. 11, 4458 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Scarlett, J. M. et al. Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents. Nat. Med. 22, 800–806 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Brown, J. M. et al. The hypothalamic arcuate nucleus-median eminence is a target for sustained diabetes remission induced by fibroblast growth factor 1. Diabetes 68, 1054–1061 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Samms, R. J. et al. Antibody-mediated inhibition of the FGFR1c isoform induces a catabolic lean state in Siberian hamsters. Curr. Biol. 25, 2997–3003 (2015).

    Article  CAS  PubMed  Google Scholar 

  104. Kim, S. et al. Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance. Autophagy 16, 1200–1220 (2020).

    Article  CAS  PubMed  Google Scholar 

  105. Drucker, D. J., Habener, J. F. & Holst, J. J. Discovery, characterization, and clinical development of the glucagon-like peptides. J. Clin. Invest. 127, 4217–4227 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Imbernon, M. et al. Tanycytes control hypothalamic liraglutide uptake and its anti-obesity actions. Cell Metab. 34, 1054–1063.e7 (2022).

    Article  CAS  PubMed  Google Scholar 

  107. Gabery, S. et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight 5, e133429 (2020).

    Article  PubMed Central  Google Scholar 

  108. Rohrbach, A. et al. Ablation of glucokinase-expressing tanycytes impacts energy balance and increases adiposity in mice. Mol. Metab. 53, 101311 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Yoo, S. et al. Tanycyte ablation in the arcuate nucleus and median eminence increases obesity susceptibility by increasing body fat content in male mice. Glia 68, 1987–2000 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Fekete, C. & Lechan, R. M. Central regulation of hypothalamic–pituitary–thyroid axis under physiological and pathophysiological conditions. Endocr. Rev. 35, 159–194 (2014).

    Article  CAS  PubMed  Google Scholar 

  111. Muller-Fielitz, H. et al. Tanycytes control the hormonal output of the hypothalamic–pituitary–thyroid axis. Nat. Commun. 8, 484 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Farkas, E. et al. A glial–neuronal circuit in the median eminence regulates thyrotropin-releasing hormone-release via the endocannabinoid system. iScience 23, 100921 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Goodman, T. & Hajihosseini, M. K. Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions. Front. Neurosci. 9, 387 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Yoo, S. & Blackshaw, S. Regulation and function of neurogenesis in the adult mammalian hypothalamus. Prog. Neurobiol. 170, 53–66 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Weiss, S. et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 16, 7599–7609 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Li, J., Tang, Y. & Cai, D. IKKβ/NF-κB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nat. Cell Biol. 14, 999–1012 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Robins, S. C. et al. α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat. Commun. 4, 2049 (2013).

    Article  CAS  PubMed  Google Scholar 

  118. Goodman, T. et al. Fibroblast growth factor 10 is a negative regulator of postnatal neurogenesis in the mouse hypothalamus. Development 147, dev180950 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Recabal, A. et al. The FGF2-induced tanycyte proliferation involves a connexin 43 hemichannel/purinergic-dependent pathway. J. Neurochem. 156, 182–199 (2021).

    Article  CAS  PubMed  Google Scholar 

  120. Orellana, J. A. et al. Glucose increases intracellular free Ca2+ in tanycytes via ATP released through connexin 43 hemichannels. Glia 60, 53–68 (2012).

    Article  PubMed  Google Scholar 

  121. Lee, D. A. et al. Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat. Neurosci. 15, 700–702 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Yoo, S. et al. Control of neurogenic competence in mammalian hypothalamic tanycytes. Sci. Adv. 7, eabg3777 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Mu, W. et al. Hypothalamic Rax+ tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice. Nat. Commun. 12, 2288 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Surbhi, Wittmann, G., Low, M. J. & Lechan, R. M. Adult-born proopiomelanocortin neurons derived from Rax-expressing precursors mitigate the metabolic effects of congenital hypothalamic proopiomelanocortin deficiency. Mol. Metab. 53, 101312 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Son, J. E. et al. Irx3 and Irx5 in Ins2–Cre+ cells regulate hypothalamic postnatal neurogenesis and leptin response. Nat. Metab. 3, 701–713 (2021).

    Article  CAS  PubMed  Google Scholar 

  126. Dou, Z., Son, J. E. & Hui, C. C. Irx3 and Irx5 — novel regulatory factors of postnatal hypothalamic neurogenesis. Front Neurosci. 15, 763856 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Mirzadeh, Z. et al. Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories. Nat. Commun. 8, 13759 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Faubel, R., Westendorf, C., Bodenschatz, E. & Eichele, G. Cilia-based flow network in the brain ventricles. Science 353, 176–178 (2016).

    Article  CAS  PubMed  Google Scholar 

  129. Genzen, J. R., Yang, D., Ravid, K. & Bordey, A. Activation of adenosine A2B receptors enhances ciliary beat frequency in mouse lateral ventricle ependymal cells. Cerebrospinal Fluid Res. 6, 15 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Genzen, J. R., Platel, J. C., Rubio, M. E. & Bordey, A. Ependymal cells along the lateral ventricle express functional P2X(7) receptors. Purinergic Signal 5, 299–307 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Conductier, G. et al. Control of ventricular ciliary beating by the melanin concentrating hormone-expressing neurons of the lateral hypothalamus: a functional imaging survey. Front. Endocrinol. 4, 182 (2013).

    Article  Google Scholar 

  132. Noble, E. E. et al. Control of feeding behavior by cerebral ventricular volume transmission of melanin-concentrating hormone. Cell Metab. 28, 55–68 e57 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Al-Massadi, O. et al. Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis. Nat. Rev. Endocrinol. 17, 745–755 (2021).

    Article  CAS  PubMed  Google Scholar 

  134. Zilkha-Falb, R., Kaushansky, N. & Ben-Nun, A. The median eminence, a new oligodendrogenic niche in the adult mouse brain. Stem Cell Rep. 14, 1076–1092 (2020).

    Article  CAS  Google Scholar 

  135. Marsters, C. M. et al. Oligodendrocyte development in the embryonic tuberal hypothalamus and the influence of Ascl1. Neural Dev. 11, 20 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Kohnke, S. et al. Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence. Cell Rep. 36, 109362 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Ren, Z. et al. Conditional knockout of leptin receptor in neural stem cells leads to obesity in mice and affects neuronal differentiation in the hypothalamus early after birth. Mol. Brain 13, 109 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Alonge, K. M. et al. Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats. Nat. Metab. 2, 1025–1033 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Lee, Y. et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487, 443–448 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Saab, A. S. et al. Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism. Neuron 91, 119–132 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Ou, Z. et al. A GPR17–cAMP–lactate signaling axis in oligodendrocytes regulates whole-body metabolism. Cell Rep. 26, 2984–2997 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Ren, H. et al. FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell 149, 1314–1326 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Ren, H., Cook, J. R., Kon, N. & Accili, D. Gpr17 in AgRP neurons regulates feeding and sensitivity to insulin and leptin. Diabetes 64, 3670–3679 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Le Thuc, O. et al. Hypothalamic inflammation and energy balance disruptions: spotlight on chemokines. Front Endocrinol. 8, 197 (2017).

    Article  Google Scholar 

  145. Wisse, B. E. et al. Evidence that lipopolysaccharide-induced anorexia depends upon central, rather than peripheral, inflammatory signals. Endocrinology 148, 5230–5237 (2007).

    Article  CAS  PubMed  Google Scholar 

  146. Jang, P. G. et al. NF-κB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia. J. Biol. Chem. 285, 9706–9715 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Jin, S. et al. Hypothalamic TLR2 triggers sickness behavior via a microglia–neuronal axis. Sci. Rep. 6, 29424 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Le Thuc, O. et al. Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation. EMBO Rep. 17, 1738–1752 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Pan, W. et al. Cytokine signaling modulates blood–brain barrier function. Curr. Pharm. Des. 17, 3729–3740 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Banks, W. A. Anorectic effects of circulating cytokines: role of the vascular blood–brain barrier. Nutrition 17, 434–437 (2001).

    Article  CAS  PubMed  Google Scholar 

  151. Valdearcos, M. et al. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep. 9, 2124–2138 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kim, F. et al. Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler. Thromb. Vasc. Biol. 28, 1982–1988 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 497, 211–216 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Heiss, C. N. et al. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Rep. 35, 109163 (2021).

    Article  CAS  PubMed  Google Scholar 

  155. Kim, J. D., Yoon, N. A., Jin, S. & Diano, S. Microglial UCP2 mediates inflammation and obesity induced by high-fat feeding. Cell Metab. 30, 952–962 e955 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Dorfman, M. D. et al. Sex differences in microglial CX3CR1 signalling determine obesity susceptibility in mice. Nat. Commun. 8, 14556 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Cansell, C. et al. Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein-positive cells and microglia in male mice. Glia 69, 42–60 (2021).

    Article  CAS  PubMed  Google Scholar 

  158. Chowen, J. A., Argente-Arizon, P., Freire-Regatillo, A. & Argente, J. Sex differences in the neuroendocrine control of metabolism and the implication of astrocytes. Front. Neuroendocrinol. 48, 3–12 (2018).

    Article  CAS  PubMed  Google Scholar 

  159. Binder, A. K. et al. Steroid Receptors in the Uterus and Ovary (Academic Press, 2015).

  160. Giacobini, P. et al. Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. PLoS Biol. 12, e1001808 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Prevot, V., Cornea, A., Mungenast, A., Smiley, G. & Ojeda, S. R. Activation of erbB-1 signaling in tanycytes of the median eminence stimulates transforming growth factor β1 release via prostaglandin E2 production and induces cell plasticity. J. Neurosci. 23, 10622–10632 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Asarian, L. & Geary, N. Modulation of appetite by gonadal steroid hormones. Philos. Trans. R. Soc. Lond. B Biol. Sci. 361, 1251–1263 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Prevot, V. et al. Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes. J. Neurosci. 23, 230–239 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Pellegrino, G. et al. GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation. Nat. Neurosci. 24, 1660–1672 (2021).

    Article  CAS  PubMed  Google Scholar 

  165. Zeng, F., Wang, Y., Kloepfer, L. A., Wang, S. & Harris, R. C. ErbB4 deletion predisposes to development of metabolic syndrome in mice. Am. J. Physiol. Endocrinol. Metab. 315, E583–E593 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Day, F. R. et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat. Commun. 6, 8464 (2015).

    Article  CAS  PubMed  Google Scholar 

  167. Prevot, V. & Sharif, A. The polygamous GnRH neuron: astrocytic and tanycytic communication with a neuroendocrineneuronal population. J. Neuroendocrinol. 34, e13104 (2020).

    Google Scholar 

  168. Swamydas, M., Bessert, D. & Skoff, R. Sexual dimorphism of oligodendrocytes is mediated by differential regulation of signaling pathways. J. Neurosci. Res. 87, 3306–3319 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Cerghet, M. et al. Proliferation and death of oligodendrocytes and myelin proteins are differentially regulated in male and female rodents. J. Neurosci. 26, 1439–1447 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Yasuda, K. et al. Sex-specific differences in transcriptomic profiles and cellular characteristics of oligodendrocyte precursor cells. Stem Cell Res. 46, 101866 (2020).

    Article  CAS  PubMed  Google Scholar 

  171. Marraudino, M. et al. G-protein-coupled estrogen receptor immunoreactivity in the rat hypothalamus is widely distributed in neurons, astrocytes, and oligodendrocytes, fluctuates during the estrous cycle, and is sexually dimorphic. Neuroendocrinology 111, 660–677 (2021).

    Article  CAS  PubMed  Google Scholar 

  172. Villa, A. et al. Sex-specific features of microglia from adult mice. Cell Rep. 23, 3501–3511 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Guneykaya, D. et al. Transcriptional and translational differences of microglia from male and female brains. Cell Rep. 24, 2773–2783 (2018).

    Article  CAS  PubMed  Google Scholar 

  174. Tramunt, B. et al. Sex differences in metabolic regulation and diabetes susceptibility. Diabetologia 63, 453–461 (2020).

    Article  PubMed  Google Scholar 

  175. Ludwig, M. Q. et al. A genetic map of the mouse dorsal vagal complex and its role in obesity. Nat. Metab. 3, 530–545 (2021).

    Article  CAS  PubMed  Google Scholar 

  176. Ludwig, M. Q., Todorov, P. V., Egerod, K. L., Olson, D. P. & Pers, T. H. Single-cell mapping of GLP-1 and GIP receptor expression in the dorsal vagal complex. Diabetes 70, 1945–1955 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Filippi, B. M. et al. Insulin signals through the dorsal vagal complex to regulate energy balance. Diabetes 63, 892–899 (2014).

    Article  CAS  PubMed  Google Scholar 

  178. Hayes, M. R. et al. Endogenous leptin signaling in the caudal nucleus tractus solitarius and area postrema is required for energy balance regulation. Cell Metab. 11, 77–83 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Williams, E. K. et al. Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166, 209–221 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Muller, T. D. et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 30, 72–130 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Grill, H. J. & Hayes, M. R. Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance. Cell Metab. 16, 296–309 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Hayes, M. R., Mietlicki-Baase, E. G., Kanoski, S. E. & De Jonghe, B. C. Incretins and amylin: neuroendocrine communication between the gut, pancreas, and brain in control of food intake and blood glucose. Annu. Rev. Nutr. 34, 237–260 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Reiner, D. J. et al. Astrocytes regulate GLP-1 receptor-mediated effects on energy balance. J. Neurosci. 36, 3531–3540 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Yulyaningsih, E. et al. Acute lesioning and rapid repair of hypothalamic neurons outside the blood–brain barrier. Cell Rep. 19, 2257–2271 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Luo, L. et al. Optimizing nervous system-specific gene targeting with cre driver lines: prevalence of germline recombination and influencing factors. Neuron 106, 37–65 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Pak, T., Yoo, S., Miranda-Angulo, A. L., Wang, H. & Blackshaw, S. Rax–CreERT2 knock-in mice: a tool for selective and conditional gene deletion in progenitor cells and radial glia of the retina and hypothalamus. PLoS ONE 9, e90381 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Zhou, Y. et al. Author Correction: Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance. Nat. Commun. 11, 1967 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Magnani, L. et al. Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer. Proc. Natl Acad. Sci. USA 110, E1490–E1499 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Liu, Z. et al. Short-term tamoxifen treatment has long-term effects on metabolism in high-fat diet-fed mice with involvement of Nmnat2 in POMC neurons. FEBS Lett. 592, 3305–3316 (2018).

    Article  CAS  PubMed  Google Scholar 

  190. O’Carroll, S. J., Cook, W. H. & Young, D. AAV targeting of glial cell types in the central and peripheral nervous system and relevance to human gene therapy. Front Mol. Neurosci. 13, 618020 (2020).

    Article  PubMed  CAS  Google Scholar 

  191. Howard, D. B., Powers, K., Wang, Y. & Harvey, B. K. Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro. Virology 372, 24–34 (2008).

    Article  CAS  PubMed  Google Scholar 

  192. Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S. & Roth, B. L. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc. Natl Acad. Sci. USA 104, 5163–5168 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Zhu, H. et al. Cre-dependent DREADD (designer receptors exclusively activated by designer drugs) mice. Genesis 54, 439–446 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the European Research Council (ERC) Synergy Grant WATCH (Well Aging and the Tanycytic Control of Health), No 810331 to R. N., V. P. and M. S.

Author information

Authors and Affiliations

Authors

Contributions

S. N. and V. P. designed the structure of the Review. S. N. wrote the first draft. R. N., M. S. and V. P. discussed and edited the manuscript.

Corresponding author

Correspondence to Vincent Prevot.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nampoothiri, S., Nogueiras, R., Schwaninger, M. et al. Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis. Nat Metab 4, 813–825 (2022). https://doi.org/10.1038/s42255-022-00610-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42255-022-00610-z

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing