Molecular and Cellular Biochemistry

, Volume 412, Issue 1–2, pp 269–280 | Cite as

Transgenerational effects of obesity and malnourishment on diabetes risk in F2 generation

  • Mervat Y. Hanafi
  • Moustafa M. Saleh
  • Mohamed I. Saad
  • Taha M. Abdelkhalek
  • Maher A. Kamel


Transgenerational inheritance of various diseases and phenotypes has been demonstrated in diverse species and involves various epigenetic markers. Obesity and malnourishment are nutritional stresses that have effects on offspring through increasing their risk of diabetes and/or obesity. Obesity and malnourishment both affect glucose metabolism and alter oxidative stress parameters in key organs. We induced obesity and malnutrition in F0 female rats by the use of obesogenic diet and protein-deficient diet, respectively. F0 obese and malnourished females were mated with control males and their offspring (F1 generation) were maintained on control diets. The male and female F1 offspring were mated with controls and the resultant offspring (F2 generation) were maintained on control diet. Glucose-sensing markers, glucose metabolism, indicators of insulin resistance and oxidative stress parameters were assessed during fetal development and till the adulthood of the offspring. Glucose-sensing genes were significantly over-expressed in distinct fetal tissues of F2 offspring of malnourished F1 females (F2-MF1F), specifically in fetal pancreas, liver, and adipose tissue. Nuclear and mitochondrial 8-oxo-dG DNA content was significantly elevated in F2-MF1F fetal pancreas. Maternal FBG was significantly elevated in F2-MF1F and F2 offspring of obese F1 females (F2-OF1F) during pregnancy. Males and females offspring of F2-OF1 exhibited significantly elevated FBG and impaired OGTT. Offspring of F2-MF1F showed similar results, while that of F2-MF1M did not significantly deviate from controls. F2-OF1F and F2-MF1F offspring exhibited significant deviation in insulin levels and HOMA-IR levels from controls. Malnourishment has a stronger transgenerational effect through maternal line compared to obesity and malnourishment through paternal line in increasing risk of diabetes in F2 generation.


Obesity Malnutrition Transgenerational inheritance Glucose sensing Oxidative stress 



Control diets


Control F1 generation


Fasting blood glucose


F2 offspring of control pregnancy


F2 offspring of OF1 males


F2 offspring of OF1 females


F2 offspring of MF1 males


F2 offspring of MF1 females


Glucose transporter 2




Homeostatic model assessment of insulin resistance


Insulin-like growth factor II


Malnourished F1 generation


Mitochondrial transcription factor A


Mitochondrial DNA


Obese F1 generation


Oral glucose tolerance test


8-Oxo-deoxy guanine


Postnatal day


Uncoupling protein 2



This study is part of a project entitled “Intra-Uterine programming of adult diabetes: an experimental study” supported by the Science and Technology Development Fund (STDF)—Egypt.

Author’s contribution

Maher A. Kamel has conceived and designed the study, carried out the analysis of data, and contributed to the writing and revision of the manuscript. Mervat Y. Hanafi, Moustafa M. Saleh, Mohamed I. Saad, and Taha M. Abdelkhalek have conducted most of the laboratory investigations and contributed to the writing and revision of the manuscript. All authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

None declared.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Biochemistry, Medical Research InstituteAlexandria UniversityAlexandriaEgypt
  2. 2.Department of Human Genetics, Medical Research InstituteAlexandria UniversityAlexandriaEgypt
  3. 3.The Ritchie Centre, Hudson Institute of Medical ResearchMonash UniversityMelbourneAustralia

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