Metabolic Brain Disease

, Volume 33, Issue 6, pp 2059–2063 | Cite as

Leptin stimulates the release of pro-inflammatory cytokines in hypothalamic astrocyte cultures from adult and aged rats

  • Camila Leite Santos
  • Larissa Daniele Bobermin
  • Diogo Onofre Souza
  • André Quincozes-SantosEmail author
Short Communication


Leptin is an adipose tissue-derived hormone that acts on the hypothalamus in order to maintain energy homeostasis. However, leptin can also induce an inflammatory response. Increasing evidence has highlighted a critical role of astrocytes in the effects of leptin on the hypothalamus. In addition, astrocytes participate in neuroinflammation by producing and releasing a wide range of inflammatory mediators. In this study, we aimed to investigate the age-dependent effect of leptin on pro- and anti-inflammatory cytokines released by the hypothalamic astrocyte cultures obtained from newborn, adult, and aged Wistar rats. In hypothalamic astrocytes from newborn rats, leptin did not change the release of pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). On the other contrary, leptin increased the release of both TNF-α and IL-1β in astrocyte cultures from adult and aged animals. Regarding the anti-inflammatory cytokine interleukin 10 (IL-10), we did not observe any change in response to leptin. In conclusion, our data suggests a pro-inflammatory action of leptin on the hypothalamus during aging. This in turn may be related to the triggering of metabolic disorders, as both of these conditions are associated with neuroinflammation.


Astrocytes Hypothalamus Leptin Inflammatory response 



This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Universidade Federal do Rio Grande do Sul, and Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção (INCTEN/CNPq).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abella V, Scotece M, Conde J et al (2017) Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat Rev Rheumatol 13:100–109. CrossRefPubMedGoogle Scholar
  2. Allison MB, Myers MG (2014) Connecting leptin signaling to biological function. J Endocrinol 223:T25–T35. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bélanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14:724–738. CrossRefPubMedGoogle Scholar
  4. Cheunsuang O, Morris R (2005) Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors. Glia 52:228–233. CrossRefPubMedGoogle Scholar
  5. Fuente-Martín E, García-Cáceres C, Granado M et al (2012) Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest 122:3900–3913. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Gainsford T, Willson TA, Metcalf D et al (1996) Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A 93:14564–14568CrossRefGoogle Scholar
  7. Garcia JM, Stillings SA, Leclerc JL et al (2017) Role of Interleukin-10 in acute brain injuries. Front Neurol 8:244. CrossRefPubMedPubMedCentralGoogle Scholar
  8. García-Cáceres C, Fuente-Martín E, Burgos-Ramos E et al (2011) Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels. Endocrinology 152:1809–1818. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gupta S, Agrawal S, Gollapudi S (2013) Increased activation and cytokine secretion in B cells stimulated with leptin in aged humans. Immun Ageing A 10:3. CrossRefGoogle Scholar
  10. He ML, Lv ZY, Shi X et al (2017) Interleukin-10 release from astrocytes suppresses neuronal apoptosis via the TLR2/NFκB pathway in a neonatal rat model of hypoxic-ischemic brain damage. J Neurochem. CrossRefGoogle Scholar
  11. Holmin S, Mathiesen T (2000) Intracerebral administration of interleukin-1beta and induction of inflammation, apoptosis, and vasogenic edema. J Neurosurg 92:108–120. CrossRefPubMedGoogle Scholar
  12. Jensen CJ, Massie A, De Keyser J (2013) Immune players in the CNS: the astrocyte. J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol 8:824–839. CrossRefGoogle Scholar
  13. Jiang T, Cadenas E (2014) Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell 13:1059–1067. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Kälin S, Heppner FL, Bechmann I et al (2015) Hypothalamic innate immune reaction in obesity. Nat Rev Endocrinol 11:339–351. CrossRefPubMedGoogle Scholar
  15. Kim JG, Suyama S, Koch M et al (2014) Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat Neurosci 17:908–910. CrossRefPubMedGoogle Scholar
  16. Koga S, Kojima A, Ishikawa C et al (2014) 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 71:180–192. CrossRefPubMedGoogle Scholar
  17. Ma XH, Muzumdar R, Yang XM et al (2002) Aging is associated with resistance to effects of leptin on fat distribution and insulin action. J Gerontol A Biol Sci Med Sci 57:B225–B231CrossRefGoogle Scholar
  18. Morselli E, Fuente-Martin E, Finan B et al (2014) Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα. Cell Rep 9:633–645. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–431. CrossRefPubMedGoogle Scholar
  20. Pinteaux E, Inoue W, Schmidt L et al (2007) Leptin induces interleukin-1beta release from rat microglial cells through a caspase 1 independent mechanism. J Neurochem 102:826–833. CrossRefPubMedGoogle Scholar
  21. Rostás I, Tenk J, Mikó A et al (2016) Age-related changes in acute central leptin effects on energy balance are promoted by obesity. Exp Gerontol 85:118–127. CrossRefPubMedGoogle Scholar
  22. Rottkamp DM, Rudenko IA, Maier MT et al (2015) Leptin potentiates astrogenesis in the developing hypothalamus. Mol Metab 4:881–889. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Santos CL, Roppa PHA, Truccolo P et al (2018) Age-dependent neurochemical remodeling of hypothalamic astrocytes. Mol Neurobiol 55:5565–5579. CrossRefPubMedGoogle Scholar
  24. Strle K, Zhou JH, Shen WH et al (2001) Interleukin-10 in the brain. Crit Rev Immunol 21:427–449CrossRefGoogle Scholar
  25. Suzukawa M, Nagase H, Ogahara I et al (2011) Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils. J Immunol Baltim Md 1950 186:5254–5260. CrossRefGoogle Scholar
  26. Valdearcos M, Xu AW, Koliwad SK (2015) Hypothalamic inflammation in the control of metabolic function. Annu Rev Physiol 77:131–160. CrossRefPubMedGoogle Scholar
  27. Wang Y, Hsuchou H, He Y et al (2015) Role of astrocytes in leptin signaling. J Mol Neurosci MN 56:829–839. CrossRefPubMedGoogle Scholar
  28. Wohleb ES, Godbout JP (2013) Basic aspects of the immunology of neuroinflammation. Mod Trends Pharmacopsychiatry 28:1–19. CrossRefPubMedGoogle Scholar
  29. Zarkesh-Esfahani H, Pockley G, Metcalfe RA et al (2001) High-dose leptin activates human leukocytes via receptor expression on monocytes. J Immunol Baltim Md 1950 167:4593–4599Google Scholar
  30. Zhang G, Li J, Purkayastha S et al (2013) Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 497:211–216. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Camila Leite Santos
    • 1
  • Larissa Daniele Bobermin
    • 1
  • Diogo Onofre Souza
    • 1
    • 2
  • André Quincozes-Santos
    • 1
    • 2
    Email author
  1. 1.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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