High-fat diet consumption during pregnancy and lactation alters NOTCH1 signaling pathway in mice offspring

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

San Diego ? CA/USA

Congreso; 97th Annual Meeting of Endrocrine Society - ENDO 2015; 2015

Annual Meeting of Endrocrine Society - ENDO 2015

High-fat diet consumption during pregnancy and lactation alters NOTCH1 signaling pathway in mice offspringStudies show that hypothalamic neural stem cells (htNSCs) play an important role in the energetic homeostasis, since they are essential for hypothalamic neurogenesis. Inflammation triggered by high-fat diet-induced (HFD) obesity seems to impair hypothalamic neurogenesis mainly through of NOTCH1 signaling. In addition, maternal consumption of HFD during the pregnancy cause metabolic disturbs in adult offspring. The aim of this study was to evaluate the effects of the maternal HFD consumption on the NOTCH1 signaling in the hypothalamus of mice offspring. Females mice (Swiss) were maintained in individual cages, with water and diet ad libitum, in a room with controlled temperature (22-24°C) and a light/dark cycle (12h). Females mice were randomly divided into two groups: one was fed with HFD and the other, with standard chow diet (SC), during pregnancy and lactation. After delivery the litter size (SC offspring, SC-O; HFD offspring, HFD-O) was reduced to 8 animals per dams. A group of dams was euthanized at the 12th day of gestation, the hypothalamus was collected to evaluate gene expression and content of TNF-alpha (by qPCR and Western Blot - WB). The offspring was evaluated in different ages (neonates ? P0 and 28 days old ? P28). Pups were weighed, euthanized and the hypothalamus was collected to evaluate gene expression and content of NOTCH1, MASH1 and HES5 proteins by qPCR and WB. Data are expressed as means  SD, the groups were compared with the Student?s t-test. Statistical significance for all analysis was set at p0.05. Hypothalamic Tnf gene expression (HFD=246.9187.13, n=4 vs. SC=1006.35%, n=3; p0.05) and the protein level of TNF- (HFD=1.510.15, n=4 vs. SC=1.000.10 arbitrary units, n=3; p0.05) were higher in the HFD than SC dams mice. Notch1 (HFD-O=78.9121.75, n=7 vs. SC-O=10011.09%, n=7; p0.05), Hes5 (HFD-O=47.2722.68, n=5 vs. SC-O=10031.45%, n=5; p0.05) and Ascl1 (HFD-O=71.4410.59, n=6 vs. SC-O=10022.22%, n=7; p0.05) gene expression was lower in the HFD-O compared to SC-O P0 mice. MASH1 protein content (HFD-O=0.210.14, n=3 vs. SC-O=0.990.03 arbitrary units, n=3; p0.001) was lower in the HFD-O than SC-O P0 mice, but NOTCH1 and HES5 protein levels were not different between groups. Hes5 gene expression (HFD-O=226.2157.61, n=7 vs. SC-O=10034.63%, n=6; p0.001) was higher in the HFD-O compared to SC-O P28 mice. However, Ascl1 gene expression (HFD-O=71.4410.59, n=7 vs. SC-O=10022.22%, n=6; p0.05) was lower in the HFD-O than SC-O P28 mice and the gene expression of Notch1 was not different between groups. However, no difference was observed in the protein level of NOTCH1, HES5 and MASH1. This study suggests that maternal HFD consumption influences NOTCH1 signaling, can lead to alterations on the cellular differentiation and maintenance of neural progenitors. These events can be related to metabolic disorders that are associated to obesity development in adulthood.Sources of research support: CAPES, CNPq and FAPESP.https://doi.org/10.1093/edrv/36.supp.1