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

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Abstract

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.

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Abbreviations

CD:

Control diets

CF1:

Control F1 generation

FBG:

Fasting blood glucose

F2-CF1:

F2 offspring of control pregnancy

F2-OF1M:

F2 offspring of OF1 males

F2-OF1F:

F2 offspring of OF1 females

F2-MF1M:

F2 offspring of MF1 males

F2-MF1F:

F2 offspring of MF1 females

GLUT2:

Glucose transporter 2

GK:

Glucokinase

HOMA-IR:

Homeostatic model assessment of insulin resistance

IGF-II:

Insulin-like growth factor II

MF1:

Malnourished F1 generation

mtTFA:

Mitochondrial transcription factor A

mtDNA:

Mitochondrial DNA

OF1:

Obese F1 generation

OGTT:

Oral glucose tolerance test

8-Oxo-dG:

8-Oxo-deoxy guanine

PND:

Postnatal day

UCP2:

Uncoupling protein 2

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Biochemistry, Medical Research Institute, Alexandria University, 165 Elhorreya Avenue, P.O. Box 21561, Alexandria, Egypt

    Mervat Y. Hanafi, Mohamed I. Saad & Maher A. Kamel

  2. Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt

    Moustafa M. Saleh & Taha M. Abdelkhalek

  3. The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, VIC, Australia

    Mohamed I. Saad

Authors
  1. Mervat Y. Hanafi
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  2. Moustafa M. Saleh
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Correspondence to Mohamed I. Saad.

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Hanafi, M.Y., Saleh, M.M., Saad, M.I. et al. Transgenerational effects of obesity and malnourishment on diabetes risk in F2 generation. Mol Cell Biochem 412, 269–280 (2016). https://doi.org/10.1007/s11010-015-2633-6

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  • DOI: https://doi.org/10.1007/s11010-015-2633-6

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