HYPOTHALAMIC MASH1 AND POMC CELL POPULATION IN OFFSPRING ARE MODULATED BY MATERNAL CONSUMPTION OF HIGH-FAT DIET DURING PREGNANCY

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

São Paulo -SP

Simposio; 3rd Prof. Eric A. Newsholme Research Symposium - Metabolic Regulation; 2016

Introduction: Studies show that inflammation triggered by high-fat diet-induced (HFD) obesity seems to impair hypothalamic neurogenesis Mash1-mediated. In addition, maternal consumption of HFD during the pregnancy cause metabolic disturbs in adult offspring. 2) Aim: To evaluate the effects of the maternal HFD consumption on Mash1 in the hypothalamus of mice offspring. 3) Methodology: Females mice (Swiss) were randomly divided into two groups: one was fed with HFD and other, with standard chow (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. Pups (28 days old-P28) were euthanized and the hypothalamus was collected to evaluate gene expression of MASH1 (Ascl1) and Hes5 by qPCR. The hypothalamic arcuate nucleus (ARC) of P28 mice was collected by punch to evaluate the same genes. The number of POMC and NPY neurons in the ARC was evaluated by immunofluorescence. Data are expressed as means  SEM, the groups were compared with the Student?s t-test. Statistical significance for all analysis was set at p0.05. 4) Results: The body weight (g) and hypothalamic mRNA levels of Il-1 were higher in HFD-O than SC-O mice. Hypothalamic mRNA levels of Hes5 (HFD-O=278.423.11, n=6 vs. SC-O=1004.45%, n=5; p=0.0001) was higher in HFD-O compared to SC-O and hypothalamic mRNA levels of Ascl1 (HFD-O=71.444.32, n=6 vs. SC-O=1008.4%, n=7; p=0.0153) was lower in HFD-O than SC-O P28 mice. In the ARC, levels of Hes5 mRNA (HFD-O=136.66.93, n=5 vs. SC-O=1006.26%, n=4; p=0.0066) was higher in HFD-O than SC-O mice and levels of Ascl1 mRNA (HFD-O=70.613.62, n=5 vs. SC-O=1009.29%, n=5; p=0.0185) was lower in HFD-O compared to SC-O mice. The number of POMC cells in ARC was diminished in HFD-O compared to SC-O (HFD-O=5.171.01, n=3 vs. SC-O=13.172.59, n=3; p=0.0451), while the number of NPY cells in ARC was higher in HFD-O than SC-O mice (HFD-O=43.365.45, n=3 vs. SC-O=19.843.32, n=3; p=0.0113). 5) Conclusion: The reduction in the levels of Mash1 mRNA could be related to modification of POMC and NPY neuron population in ARC. This scenario contributes to hyperphagia, weight gain, and could be responsible by development of obesity in adulthood.Financial support: CAPES, CNPq and FAPESP.