Skip to main content Accessibility help

Role of hypothalamic tanycytes in nutrient sensing and energy balance

  • Marco Travaglio (a1) and Francis J. P. Ebling (a1)


Animal models are valuable for the study of complex behaviours and physiology such as the control of appetite because genetic, pharmacological and surgical approaches allow the investigation of underlying mechanisms. However, the majority of such studies are carried out in just two species, laboratory mice and rats. These conventional laboratory species have been intensely selected for high growth rate and fecundity, and have a high metabolic rate and short lifespan. These aspects limit their translational relevance for human appetite control. This review will consider the value of studies carried out in a seasonal species, the Siberian hamster, which shows natural photoperiod-regulated annual cycles in appetite, growth and fattening. Such studies reveal that this long-term control is not simply an adjustment of the known hypothalamic neuronal systems that control hunger and satiety in the short term. Long-term cyclicity is probably driven by hypothalamic tanycytes, glial cells that line the ventricular walls of the hypothalamus. These unique cells sense nutrients and metabolic hormones, integrate seasonal signals and effect plasticity of surrounding neural circuits through their function as a stem cell niche in the adult. Studies of glial cell function in the hypothalamus offer new potential for identifying central targets for appetite and body weight control amenable to dietary or pharmacological manipulation.


Corresponding author

*Corresponding author: Francis J. P. Ebling, email


Hide All
1.Ebling, FJ (2015) Hypothalamic control of seasonal changes in food intake and body weight. Front Neuroendocrinol 37, 97107.
2.Ebling, FJP & Barrett, P (2008) The regulation of seasonal changes in food intake and body weight. J Neuroendocrinol 20, 827833.
3.Reddy, AB, Cronin, AS, Ford, H et al. (1999) Seasonal regulation of food intake and body weight in the male Siberian hamster: studies of hypothalamic orexin (hypocretin), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC). Eur J Neurosci 11, 32553264.
4.Ebling, FJP, Arthurs, OJ, Turney, BW et al. (1998) Seasonal neuroendocrine rhythms in the male Siberian hamster persist following monosodium glutamate-induced lesions of the arcuate nucleus in the neonatal period. J Neuroendocrinol 10, 701712.
5.Mercer, JG, Lawrence, CB, Moar, KM et al. (1997) Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF mRNA in Djungarian hamsters. Am J Physiol 273, R768R776.
6.Rousseau, K, Atcha, Z, Cagampang, FRA et al. (2002) Photoperiodic regulation of leptin resistance in the seasonally breeding Siberian hamster (Phodopus sungorus). Endocrinology 143, 30833095.
7.Barrett, P, Ivanova, E, Graham, ES et al. (2006) Photoperiodic regulation of GPR50, Nestin and CRBP1 in tanycytes of the third ventricle ependymal layer of the Siberian hamster. J Endocrinol 191, 687698.
8.Goodman, T & Hajihosseini, MK (2015) Hypothalamic tanycytes—masters and servants of metabolic, neuroendocrine, and neurogenic functions. Front Neurosci 9, 387.
9.Lewis, JE & Ebling, FJP (2017) Tanycytes as regulators of seasonal cycles in neuroendocrine function. Frontiers in Neurology 8, 79.
10.Xiong, JJ, Karsch, FJ & Lehman, MN (1997) Evidence for seasonal plasticity in the gonadotrophin-releasing hormone (GnRH) system of the ewe: changes in synaptic inputs onto GnRH neurons. Endocrinology 138, 12401250.
11.Prevot, V, Bellefontaine, N, Baroncini, M et al. (2010) Gonadotrophin-releasing hormone nerve terminals, tanycytes and neurohaemal junction remodelling in the adult median eminence: functional consequences for reproduction and dynamic role of vascular endothelial cells. J Neuroendocrinol 22, 639649.
12.Morgan, PJ & Hazlerigg, DG (2008) Photoperiodic signalling through the melatonin receptor turns full circle. J Neuroendocrinol 20, 820826.
13.Hanon, EA, Lincoln, GA, Fustin, JM et al. (2008) Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr Biol 18, 11471152.
14.Nishiwaki-Ohkawa, T & Yoshimura, T (2016) Molecular basis for regulating seasonal reproduction in vertebrates. J Endocrinol 229, R117R127.
15.Barrett, P, Ebling, FJP, Schuhler, A et al. (2007) Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction. Endocrinology 148, 36083617.
16.Murphy, M, Jethwa, PH, Warner, A et al. (2012) Effects of manipulating hypothalamic tri-iodothyronine concentrations on seasonal body weight and torpor cycles in Siberian hamsters. Endocrinology 153, 101112.
17.Helfer, G, Ross, AW, Thomson, LM et al. (2016) A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance. Sci Rep 6, 26830.
18.Helfer, G, Ross, AW & Morgan, PJ (2013) Neuromedin U partly mimics thyroid-stimulating hormone and triggers Wnt/β-catenin signalling in the photoperiodic response of F344 rats. J Neuroendocrinol 25, 12641272.
19.Shearer, KD, Goodman, TH, Ross, AW et al. (2010) Photoperiodic regulation of retinoic acid signaling in the hypothalamus. J Neurochem 112, 246257.
20.Langlet, F (2014) Tanycytes: a gateway to the metabolic hypothalamus. J Neuroendocrinol 25, 753760.
21.Rodriguez, EM, Blázquez, JL, Pastor, FE et al. (2005) Hypothalamic tanycytes: a key component of brain-endocrine interaction. Int Rev Cytol 247, 89164.
22.Balland, E, Dam, J, Langlet, F et al. (2014) Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab 19, 293301.
23.Djogo, T, Robins, SC, Schneider, S et al. (2016) Adult NG2-glia are required for median eminence-mediated leptin sensing and body weight control. Cell Metab 23, 797810.
24.Ciofi, P (2011) The arcuate nucleus as a circumventricular organ in the mouse. Neurosci Lett 487, 187190.
25.Langlet, F, Levin, BE, Luquet, S et al. (2013) Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab 17, 607617.
26.Schaeffer, M, Langlet, F, Lafont, C et al. (2016) Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons. Proc Natl Acad Sci U S A 110, 15121517.
27.Frayling, C, Britton, R & Dale, N (2011) ATP-mediated glucosensing by hypothalamic tanycytes. J Physiol 589, 22752286.
28.Orellana, JA, Saez, PJ, Cortes-Campos, C et al. (2012) Glucose increases intracellular free Ca(2+) in tanycytes via ATP released through connexin 43 hemichannels. Glia 60, 5368.
29.García, M, Millán, C, Balmaceda-Aguilera, C et al. (2003) Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing. J Neurochem 86, 709724.
30.Benford, H, Bolborea, M, Pollatzek, E et al. (2017) A sweet taste receptor-dependent mechanism of glucosensing in hypothalamic tanycytes. Glia 65, 773789.
31.Yi, CX, Habegger, KM, Chowen, JA et al. (2011) A role for astrocytes in the central control of metabolism. Neuroendocrinology 93, 143149.
32.Lazutkaite, G, Soldà, A, Lossow, K et al. (2017) Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Mol Metab 6, 14801492.
33.Lee, DA, Yoo, S, Pak, T et al. (2014) Dietary and sex-specific factors regulate hypothalamic neurogenesis in young adult mice. Front Neurosci 8, 157.
34.Severi, I, Perugini, J, Mondini, E et al. (2013) Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus. Front Neurosci 7, 263.
35.Kokoeva, MV, Yin, H & Flier, JS (2005) Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science 310, 679683.
36.Kokoeva, MV, Yin, H & Flier, JS (2007) Evidence for constitutive neural cell proliferation in the adult murine hypothalamus. J Comp Neurol 505, 209220.
37.Robins, SC, Stewart, I, McNay, DE et al. (2013) α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4, 2049.
38.Haan, N, Goodman, T, Najdi-Samiei, A et al. (2013) FGF10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J Neurosci 33, 61706180.
39.Rizzoti, K & Lovell-Badge, R (2017) Pivotal role of median eminence tanycytes for hypothalamic function and neurogenesis. Mol Cell Endocrinol 445, 713.
40.Migaud, M, Batailler, M, Pillon, D et al. (2011) Seasonal Changes in Cell Proliferation in the Adult Sheep Brain and Pars Tuberalis. J Biol Rhythms 26, 486496.
41.Huang, L, De Vries, GJ & Bittman, EL (1998) Photoperiod regulates neuronal bromodeoxyuridine labeling in the brain of a seasonally breeding mammal. J Neurobiol 36, 410420.
42.Hazlerigg, DG, Wyse, CA, Dardente, H et al. (2013) Photoperiodic variation in CD45-positive cells and cell proliferation in the mediobasal hypothalamus of the Soay sheep. Chronobiol Int 30, 548558.
43.Batailler, M, Droguerre, M, Baroncini, M et al. (2014) DCX-expressing cells in the vicinity of the hypothalamic neurogenic niche: a comparative study between mouse, sheep, and human tissues. J Comp Neurol 522, 19661985.
44.Pellegrino, G, Trubert, C, Terrien, J et al. (2018) A comparative study of the neural stem cell niche in the adult hypothalamus of human, mouse, rat and gray mouse lemur (Microcebus murinus). J Comp Neurol 526, 14191443.
45.Koopman, ACM, Taziaux, M & Bakker, J (2017) Age-related changes in the morphology of tanycytes in the human female infundibular nucleus/median eminence. J Neuroendocrinol 29, 19.
46.Zoli, M, Ferraguti, F, Frasoldati, A et al. (1995) Age-related alterations in tanycytes of the mediobasal hypothalamus of the male rat. Neurobiol Aging 16, 7783.
47.Stevenson, TJ, Visser, ME, Arnold, W et al. (2015) Disrupted seasonal biology impacts health, food security, and ecosystems. Proc Biol Sci. 282 20151453.


Role of hypothalamic tanycytes in nutrient sensing and energy balance

  • Marco Travaglio (a1) and Francis J. P. Ebling (a1)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed