Metabolic Brain Disease

, Volume 28, Issue 4, pp 721–725 | Cite as

Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life

  • Ewa K. Stachowiak
  • Malathi Srinivasan
  • Michal K. Stachowiak
  • Mulchand S. PatelEmail author
Short Communication


Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished migration and maturation of stem-like cells in the 3rd ventricular region as well as in the brain cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.


Maternal obesity High fat diet Fetal brain cellular development Hypothalamic appetite regulation 



This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-061518 (MSP).

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. Bilbo SD, Tsang V (2010) Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J 24(6):2104–2115. doi: 10.1096/fj.09-144014 PubMedCrossRefGoogle Scholar
  2. Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF (2008) Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci 28(46):12107–12119. doi: 10.1523/JNEUROSCI.2642-08.2008 PubMedCrossRefGoogle Scholar
  3. Dodds L, Fell DB, Shea S, Armson BA, Allen AC, Bryson S (2011) The role of prenatal, obstetric and neonatal factors in the development of autism. J Autism Dev Disord 41(7):891–902. doi: 10.1007/s10803-010-1114-8 PubMedCrossRefGoogle Scholar
  4. Fernandez-Twinn DS, Ozanne SE (2010) Early life nutrition and metabolic programming. Ann N Y Acad Sci 1212:78–96. doi: 10.1111/j.1749-6632.2010.05798.x PubMedCrossRefGoogle Scholar
  5. Flegal KM, Carroll MD, Ogden CL, Curtin LR (2010) Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303(3):235–241. doi: 10.1001/jama.2009.2014 PubMedCrossRefGoogle Scholar
  6. Gupta A, Srinivasan M, Thamadilok S, Patel MS (2009) Hypothalamic alterations in fetuses of high fat diet-fed obese female rats. J Endocrinol 200(3):293–300. doi: 10.1677/JOE-08-0429 PubMedCrossRefGoogle Scholar
  7. Kiyohara C, Yoshimasu K (2009) Molecular epidemiology of major depressive disorder. Environ Health Prev Med 14(2):71–87. doi: 10.1007/s12199-008-0073-6 PubMedCrossRefGoogle Scholar
  8. Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 82:1–8PubMedGoogle Scholar
  9. Palmer L, Murayama M, Larkum M (2012) Inhibitory regulation of dendritic activity in vivo. Front Neural Circ 6:26. doi: 10.3389/fncir.2012.00026 Google Scholar
  10. Poon K, Barson JR, Fagan SE, Leibowitz SF (2012) Developmental changes in embryonic hypothalamic neurons during prenatal fat exposure. Am J Physiol Endocrinol Metab 303(3):E432–E441. doi: 10.1152/ajpendo.00238.2012 PubMedCrossRefGoogle Scholar
  11. Rofey DL, Kolko RP, Iosif AM, Silk JS, Bost JE, Feng W, Szigethy EM, Noll RB, Ryan ND, Dahl RE (2009) A longitudinal study of childhood depression and anxiety in relation to weight gain. Child Psychiatry Hum Dev 40(4):517–526. doi: 10.1007/s10578-009-0141-1 PubMedCrossRefGoogle Scholar
  12. Srinivasan M, Katewa SD, Palaniyappan A, Pandya JD, Patel MS (2006) Maternal high-fat diet consumption results in fetal malprogramming predisposing to the onset of metabolic syndrome-like phenotype in adulthood. Am J Physiol Endocrinol Metab 291(4):E792–E799PubMedCrossRefGoogle Scholar
  13. Stachowiak EK, Oommen S, Vasu VT, Srinivasan M, Stachowiak M, Gohil K, Patel MS (2013) Maternal obesity affects gene expression and cellular development in fetal brains. Nutr Neurosci 16(3):96–103. doi: 10.1179/1476830512Y.0000000035 PubMedCrossRefGoogle Scholar
  14. Sullivan EL, Smith MS, Grove KL (2011) Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology 93(1):1–8. doi: 10.1159/000322038 PubMedCrossRefGoogle Scholar
  15. Waring ME, Lapane KL (2008) Overweight in children and adolescents in relation to attention-deficit/hyperactivity disorder: results from a national sample. Pediatrics 122(1):e1–e6. doi: 10.1542/peds.2007-1955 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ewa K. Stachowiak
    • 1
  • Malathi Srinivasan
    • 2
  • Michal K. Stachowiak
    • 1
  • Mulchand S. Patel
    • 2
    Email author
  1. 1.Department of Pathology and Anatomic Sciences, School of Medicine and Biomedical SciencesUniversity at Buffalo, State University of New YorkBuffaloUSA
  2. 2.Department of Biochemistry, School of Medicine and Biomedical SciencesUniversity at Buffalo, State University of New YorkBuffaloUSA

Personalised recommendations