The Effects of Leptin on Rat Brain Development; An Experimental Study

  • Arzu YayEmail author
  • Gozde Ozge Onder
  • Saim Ozdamar
  • Anzel Bahadir
  • Metin Aytekin
  • Munevver Baran


Leptin has a crucial role in the development of the brain throughout the embryonic and neonatal stages. Leptin-deficient mice have diminished total brain volume, weight, and DNA amount, which are redintegrated by the supplementation of leptin (Ahima and Osei 2004; Steppan and Swick 1999). It has been determined that maternal leptin concentration was increased in transgenic skinny mice overexpressing leptin after birth, which was associated with a lower fetal body weight compared to wild type mice (Sagawa et al. 2002). These findings suggest that leptin levels, from both the fetus and the mother, may be associated with the neonatal growth and development (Udagawa et al. 2006).

Leptin may serve as an important hormone for fetal growth. Its signaling may provide a nutritional sensing function available from the mother to fetus during pregnancy (Masuzaki et al. 1997). In normal development, it has been detected in the blood of the umbilical cord at the 18th week of gestation,...



The authors declared that this study was funded by Scientific Research Coordination Unit of Erciyes University (EUBAP, TCD-4471).

Compliance with Ethical Standards

Conflict of interest

The authors declared no conflicts of interest.


  1. Ahima RS, Flier JS (2000) Leptin. Annu Rev Physiol 62:413– 437. CrossRefGoogle Scholar
  2. Ahima RS, Osei SY (2004) Leptin signaling. Physiol Behav 81(2):223–241. CrossRefGoogle Scholar
  3. Andressen C, Stocker E, Klinz FJ, Lenka N, Hescheler J, Fleischmann B, Arnhold S, Addicks K (2001) Nestin-specific green fluorescent protein expression in embryonic stem cell-derived neural precursor cells used for transplantation. Stem Cells 19(5):419–424. CrossRefGoogle Scholar
  4. Bouret SG (2013) Organizational actions of metabolic hormones. Front Neuroendocrinol 34(1):18–26. CrossRefGoogle Scholar
  5. Cetin I, Morpurgo PS, Radaelli T, Taricco E, Cortelazzi D, Bellotti M, Pardi G, Beck-Peccoz P (2000) Fetal plasma leptin concentrations: relationship with different intrauterine growth patterns from 19 weeks to term. Pediatric Res 48(5):646–651. CrossRefGoogle Scholar
  6. Chen H, Liu J (2009) Effects of intrauterine growth limitation on perinatal brain development. Zhonghua Er Ke Za Zhi 47(1):33–35Google Scholar
  7. Chen Z, Zhao Y, Yang Y, Li Z (2011) Leptin withdrawal after birth: a neglected factor account for cognitive deficit in offspring of GDM mother. Med Hypotheses 77(1):125–127. CrossRefGoogle Scholar
  8. Chinnaiyan P, Wang M, Rojiani AM, Tofilon PJ, Chakravarti A, Ang KK, Zhang HZ, Hammond E, Curran W Jr, Mehta MP (2008) The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group. Radiat Oncol 3:1–8. 32 .CrossRefGoogle Scholar
  9. Cnattingius S, Villamor E, Johansson S, Edstedt Bonamy AK, Persson M, Wikstrom AK, Granath F (2013) Maternal obesity and risk of preterm delivery. JAMA 309(22):2362–2370. CrossRefGoogle Scholar
  10. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334(5):292–295. CrossRefGoogle Scholar
  11. Coupe B, Grit I, Hulin P, Randuineau G, Parnet P (2012) Postnatal growth after intrauterine growth restriction alters central leptin signal and energy homeostasis. PLoS ONE 7(1):e30616. CrossRefGoogle Scholar
  12. Craig J, Zhu H, Dyce PW, Wen L, Li J (2005) Leptin enhances porcine preimplantation embryo development in vitro. Mol Cell Endocrinol 229(1–2):141–147. CrossRefGoogle Scholar
  13. Djelantik AA, Kunst AE, van der Wal MF, Smit HA, Vrijkotte TG (2012) Contribution of overweight and obesity to the occurrence of adverse pregnancy outcomes in a multi-ethnic cohort: population attributive fractions for Amsterdam. BJOG 119(3):283–290. CrossRefGoogle Scholar
  14. Gohlke BC, Huber A, Bartmann P, Fimmers R, Hecher K, Bouret SG, Roth CL (2006) Cord blood leptin and IGF-I in relation to birth weight differences and head circumference in monozygotic twins. J Pediatr Endocrinol Metab 19(1):3–9. CrossRefGoogle Scholar
  15. Harigaya A, Nagashima K, Nako Y, Morikawa A (1997) Relationship between concentration of serum leptin and fetal growth. J Clin Endocrinol Metab 82(10):3281–3284. CrossRefGoogle Scholar
  16. Henson MC, Castracane VD (2000) Leptin in pregnancy. Biol Reprod 63(5):1219–1228. CrossRefGoogle Scholar
  17. Herrid M, Nguyen VL, Hinch G, McFarlane JR (2006) Leptin has concentration and stage-dependent effects on embryonic development in vitro. Reproduction 132(2):247–256. CrossRefGoogle Scholar
  18. Kawamura K, Sato N, Fukuda J, Kodama H, Kumagai J, Tanikawa H, Nakamura A, Tanaka T (2002) Leptin promotes the development of mouse preimplantation embryos in vitro. Endocrinology 143(5):1922–1931. CrossRefGoogle Scholar
  19. Koutcherov Y, Mai JK, Paxinos G (2003) Hypothalamus of the human fetus. J Chem Neuroanat 26(4):253–270. CrossRefGoogle Scholar
  20. Lane RH, Ramirez RJ, Tsirka AE, Kloesz JL, McLaughlin MK, Gruetzmacher EM, Devaskar SU (2001) Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats. Brain Res 895(1–2):186–193. CrossRefGoogle Scholar
  21. Levay EA, Paolini AG, Govic A, Hazi A, Penman J, Kent S (2008) Anxiety-like behaviour in adult rats perinatally exposed to maternal calorie restriction. Behav Brain Res 191(2):164–172. CrossRefGoogle Scholar
  22. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K (1997) Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med 3(9):1029–1033. CrossRefGoogle Scholar
  23. Mattioli B, Giordani L, Quaranta MG, Viora M (2009) Leptin exerts an anti-apoptotic effect on human dendritic cells via the PI3K-Akt signaling pathway. FEBS Lett 583(7):1102–1106. CrossRefGoogle Scholar
  24. Moon HS, Dincer F, Mantzoros CS (2012) Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice. Diabetologia 56(3):627–634. CrossRefGoogle Scholar
  25. Pinto S, Roseberry AG, Liu H, Diano S, Shanabrough M, Cai X, Friedman JM, Horvath TL (2004) Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304(5667):110–115. CrossRefGoogle Scholar
  26. Proulx K, Clavel S, Nault G, Richard D, Walker CD (2001) High neonatal leptin exposure enhances brain GR expression and feedback efficacy on the adrenocortical axis of developing rats. Endocrinology 142(11):4607–4616. CrossRefGoogle Scholar
  27. Sagawa N, Yura S, Itoh H, Mise H, Kakui K, Korita D, Takemura M, Nuamah MA, Ogawa Y, Masuzaki H, Nakao K, Fujii S (2002) Role of leptin in pregnancy—a review. Placenta 23(16):80–86. CrossRefGoogle Scholar
  28. Sarandakou A, Protonotariou E, Rizos D, Malamitsi-Puchner A, Giannaki G, Phocas I, Creatsas G (2000) Serum leptin concentrations during the perinatal period. Am J Perinatol 17(6):325–328. CrossRefGoogle Scholar
  29. Schubring C, Englaro P, Siebler T, Blum WF, Demirakca T, Kratzsch J, Kiess W (1998) Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels. Horm Res 50(5):276–283. Google Scholar
  30. Signore AP, Zhang F, Weng Z, Gao Y, Chen J (2008) Leptin neuroprotection in the CNS: mechanisms and therapeutic potentials. J Neurochem 106(5):1977–1990. CrossRefGoogle Scholar
  31. Steppan CM, Swick AG (1999) A role of leptin in brain development. Biochem Biophys Res Commun 256(3):600–602. CrossRefGoogle Scholar
  32. Udagawa J, Hashimoto R, Suzuki H, Hatta T, Sotomaru Y, Hioki K, Kagohashi Y, Nomura T, Minami Y, Otani H (2006) The role of leptin in the development of the cerebral cortex in mouse embryos. Endocrinology 147(2):647–658. CrossRefGoogle Scholar
  33. Udagawa J, Hatta T, Hashimoto R, Otani H (2007) Roles of leptin in prenatal and perinatal brain development. Congenit Anom 47(3):77–83. CrossRefGoogle Scholar
  34. Wang T, Zhang J, Lu X, Xi W, Li Z (2011) Maternal early pregnancy body mass index and risk of preterm birth. Arch Gynecol Obstet 284(4):813–819. CrossRefGoogle Scholar
  35. Wendremaire M, Bardou M, Peyronel C, Hadi T, Sagot P, Morrison JJ, Lirussi F (2011) Effects of leptin on lipopolysaccharide-induced myometrial apoptosis in an in vitro human model of chorioamnionitis. Am J Obstet Gynecol 205(4):363. e1-363.e9.CrossRefGoogle Scholar
  36. Wood MD, MacEwan MR, French AR, Moore AM, Hunter DA, Mackinnon SE, Moran DW, Borschel GH, Sakiyama-Elbert SE (2010) Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration. Biotechnol Bioeng 106(6):970–979. CrossRefGoogle Scholar
  37. Yay A, Ozdamar S, Balcıoglu E, Baran M, Akkus D, Sonmez MF (2015) The effects of adriamycin on E-cadherin mediated cell-cell adhesion and apoptosis during early kidney development. Biotech Histochem 90(5):375–383. CrossRefGoogle Scholar
  38. Yay A, Goktepe O, Bahadir A, Ozdamar S, Oktem IS, Coruh A, Baran M (2018) Assessment of markers expressed in human hair follicles according to different skin regions. Adv Clin Exp Med 27(7):929–939. CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Arzu Yay
    • 1
    Email author
  • Gozde Ozge Onder
    • 1
  • Saim Ozdamar
    • 2
  • Anzel Bahadir
    • 3
  • Metin Aytekin
    • 4
  • Munevver Baran
    • 5
  1. 1.Department of Histology and Embryology, Faculty of MedicineErciyes UniversityKayseriTurkey
  2. 2.Department of Histology and Embryology, Faculty of MedicinePamukkale UniversityKayseriTurkey
  3. 3.Department of Biophysics, Faculty of MedicineDuzce UniversityDuzceTurkey
  4. 4.Department of Pathobiology/Lerner Research InstituteCleveland ClinicClevelandUSA
  5. 5.Department of Pharmaceutical Basic Science, Faculty of PharmacyErciyes UniversityKayseriTurkey

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