Activation of pathway of Notch signaling in hippocampus in mice offspring by maternal consumption of high-fat diet during pregnancy and lactation

MENDES DA SILVA, CRISTIANO; LEMES, SIMONE FERREIRA; PAYOLLA, TANYARA BALIANI; VERSUTTI, MILENA DIORIO; MILANSKI, MARCIANE; TORSONI, ADRIANA SOUZA; TORSONI, MARCIO ALBERTO

Sofia

Congreso; 21th European Congress on Obesity (ECO2014); 2014

Introduction: The high-fat diet (HFD) induced obesity in female mice has been used as a model for maternal obesity. Recent evidence has shown that consumption of HFD is associated with impaired hippocampus-dependent learning and memory. In addition, the activation of Notch signaling leads to up-regulation of Hes5, condition known inhibit proliferation and differentiation of neural progenitors and this can impair to hippocampal neurogenesis.Methods: Female Swiss mice were fed a control diet (CD ? 14.7% fat) or HFD (45.0% fat) throughout pre-mating until suckling. From weaning until experimental day (d28) offspring from CD or HFD received standard chow. Body weight and adipose tissue of mothers and pups also were measured. The proteins Notch1, Hes5, Mash1, Delta1 and Sirt1 in the hippocampus were assessed by RT-PCR and western blot.Results: Our findings show that dams fed HFD and your pups exhibit increased body weight gain and adipose tissue. Furthermore, under maternal feeding conditions, HFD offspring exhibited increase of Hes5 in the hippocampus when compared CD. In addition, HFD offspring alsoshowed gene expression increased of Notch1 and Hes5, while Mash1 expression was decreased. However expression of Delta1 and Sirt1 did not change significantly.Conclusion: We propose that overexpression of Hes5, known Notch effector, down-regulates expression of the proneural gene Mash1 in offspring from obese mothers, promoting slow down cell differentiation. Our results provide further evidence of molecular susceptibility offspring?shippocampus to maternal HFD and suggest that Notch1 signaling in this brain area is pivotal for neuronal differentiation.