Leptin Stimulates the Release of Pro-inflammatory Cytokines in Hypothalamic Astrocyte Cultures from Adult and Aged Rats

Overview

Journal Metab Brain Dis

Publisher Springer

Specialties Endocrinology
Neurology

Date 2018 Sep 20

PMID 30229384

Citations 16

Authors

Camila Leite Santos

Larissa Daniele Bobermin

Diogo Onofre Souza

Andre Quincozes-Santos

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics.

Evans A, Li Y Int J Mol Sci. 2024; 25(22).

PMID: 39596529 PMC: 11594459. DOI: 10.3390/ijms252212464.

Glioprotective Effects of Sulforaphane in Hypothalamus: Focus on Aging Brain.

Santos C, Weber F, Bello-Klein A, Bobermin L, Quincozes-Santos A Neurochem Res. 2024; 49(9):2505-2518.

PMID: 38886329 DOI: 10.1007/s11064-024-04196-8.

Aging changes the expression of adenosine receptors, insulin-like growth factor 1 (IGF1), and hypoxia-inducible factor 1α (HIF1α) in hypothalamic astrocyte cultures.

Santos C, Bobermin L, Quincozes-Santos A Aging Brain. 2024; 5:100104.

PMID: 38225985 PMC: 10788490. DOI: 10.1016/j.nbas.2023.100104.

Role of Senescent Astrocytes in Health and Disease.

Meldolesi J Int J Mol Sci. 2023; 24(10).

PMID: 37239843 PMC: 10218328. DOI: 10.3390/ijms24108498.

Characterizing the host response to rhPDGF-BB in a rat spinal arthrodesis model.

Yamaguchi J, Weiner J, Minardi S, Greene A, Ellenbogen D, Hallman M JOR Spine. 2022; 4(4):e1173.

PMID: 35005440 PMC: 8717117. DOI: 10.1002/jsp2.1173.

References

Suzukawa M, Nagase H, Ogahara I, Han K, Tashimo H, Shibui A . Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils. J Immunol. 2011; 186(9):5254-60. DOI: 10.4049/jimmunol.1004054. View

Rottkamp D, Rudenko I, Maier M, Roshanbin S, Yulyaningsih E, Perez L . Leptin potentiates astrogenesis in the developing hypothalamus. Mol Metab. 2015; 4(11):881-9. PMC: 4632125. DOI: 10.1016/j.molmet.2015.08.005. View

Gainsford T, Willson T, Metcalf D, Handman E, McFarlane C, Ng A . Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A. 1996; 93(25):14564-8. PMC: 26173. DOI: 10.1073/pnas.93.25.14564. View

Wohleb E, Godbout J . Basic aspects of the immunology of neuroinflammation. Mod Trends Pharmacopsychiatry. 2014; 28:1-19. DOI: 10.1159/000343964. View

He M, Lv Z, Shi X, Yang T, Zhang Y, Li T . 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. 2017; 142(6):920-933. DOI: 10.1111/jnc.14126. View

Abella V, Scotece M, Conde J, Pino J, Gonzalez-Gay M, Gomez-Reino J . Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat Rev Rheumatol. 2017; 13(2):100-109. DOI: 10.1038/nrrheum.2016.209. View

Pinteaux E, Inoue W, Schmidt L, Molina-Holgado F, Rothwell N, Luheshi G . Leptin induces interleukin-1beta release from rat microglial cells through a caspase 1 independent mechanism. J Neurochem. 2007; 102(3):826-33. DOI: 10.1111/j.1471-4159.2007.04559.x. View

Perea G, Navarrete M, Araque A . Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 2009; 32(8):421-31. DOI: 10.1016/j.tins.2009.05.001. View

Santos C, Roppa P, Truccolo P, Fontella F, Souza D, Bobermin L . Age-Dependent Neurochemical Remodeling of Hypothalamic Astrocytes. Mol Neurobiol. 2017; 55(7):5565-5579. DOI: 10.1007/s12035-017-0786-x. View

10.

Belanger M, Allaman I, Magistretti P . Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 2011; 14(6):724-38. DOI: 10.1016/j.cmet.2011.08.016. View

11.

Kim J, Suyama S, Koch M, Jin S, Argente-Arizon P, Argente J . Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. Nat Neurosci. 2014; 17(7):908-10. PMC: 4113214. DOI: 10.1038/nn.3725. View

12.

Strle K, Zhou J, Shen W, Broussard S, Johnson R, Freund G . Interleukin-10 in the brain. Crit Rev Immunol. 2002; 21(5):427-49. View

13.

Gupta S, Agrawal S, Gollapudi S . Increased activation and cytokine secretion in B cells stimulated with leptin in aged humans. Immun Ageing. 2013; 10(1):3. PMC: 3557206. DOI: 10.1186/1742-4933-10-3. View

14.

Allison M, Myers Jr M . 20 years of leptin: connecting leptin signaling to biological function. J Endocrinol. 2014; 223(1):T25-35. PMC: 4170570. DOI: 10.1530/JOE-14-0404. View

15.

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. 2014; 71:180-92. DOI: 10.1016/j.nbd.2014.08.015. View

16.

Morselli E, Fuente-Martin E, Finan B, Kim M, Frank A, Garcia-Caceres C . Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα. Cell Rep. 2014; 9(2):633-45. PMC: 4223650. DOI: 10.1016/j.celrep.2014.09.025. View

17.

Ma X, Muzumdar R, Yang X, Gabriely I, Berger R, Barzilai N . Aging is associated with resistance to effects of leptin on fat distribution and insulin action. J Gerontol A Biol Sci Med Sci. 2002; 57(6):B225-31. DOI: 10.1093/gerona/57.6.b225. View

18.

Cheunsuang O, Morris R . 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. 2005; 52(3):228-33. DOI: 10.1002/glia.20239. View

19.

Rostas I, Tenk J, Miko A, Furedi N, Soos S, Solymar M . Age-related changes in acute central leptin effects on energy balance are promoted by obesity. Exp Gerontol. 2016; 85:118-127. DOI: 10.1016/j.exger.2016.10.006. View

20.

Jensen C, Massie A, De Keyser J . Immune players in the CNS: the astrocyte. J Neuroimmune Pharmacol. 2013; 8(4):824-39. DOI: 10.1007/s11481-013-9480-6. View