ABSTRACT
The altered maternal/fetal metabolism appears to be associated with a diabetogenic effect in the adult offspring even in the absence of genetic predisposition. Aim: The study aimed to investigate the effect of maternal obesity and malnutrition on the peripheral glucose sensing and mitochondria biogenesis in F1 offspring. Effect of postnatal diet was also evaluated. Methods: Three groups of female Wistar rats were used (control, obese and malnourished). After the pregnancy and delivery the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks OGTT was constructed and serum and tissues were obtained for assessment of glucose homeostasis parameters, mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (Phosho-IR) and GLUT4. Results: The results indicated that maternal obesity impair glucose tolerance and sensing in the offspring from the 15th week of age even under control diet and the situation is worse under HCD these defects were preceded by significant decline in mtDNA copy number in muscle and adipose tissues as early as 5th week of age. The offspring of malnourished mothers show normal and even better glucose tolerance and sensing and normal mtDNA copy number under control diet, while those offspring under HCD show impaired glucose sensing and tolerance only at older age than obese group. Conclusion: maternal obesity and malnutrition differentially affect glucose sensing and tolerance, mtDNA copy number and the expression of genes involved in the mitochondrial biogenesis and function in the muscles and adipose tissues in the F1 offspring with the postnatal feeding appearing to play a central role in these differential effects. The male F1 offspring appear to be more sensitive for fetal diabetogenic programming than female offspring.