Maternal obesity alters neurotrophin-associated MAPK ignaling in the hypothalamus of male mouse offspring

In the present project we examined the effects of maternal obesity to offspring hypothalamic tissue at postnatal day (P) 21. Maternal obesity has emerged as an important risk factor for the development of metabolic disorders in the offspring.To obtain an overview of affected genes in the offsprings hypothalamus, the center of hunger and satiety in the brain, we performed whole genome microarray expression profiling. Female mice were fed either a control diet (SD) or a high fat diet (HFD) after weaning until mating and during pregnancy and gestation. On P21, male pups were sacrificed and blood samples were collected for further analyses. The hypothalamus was cut immediately caudal to the optic chiasm. The dissection was limited laterally by the hypothalamic sulci and dorsally by the mammillothalamic tract. Hypothalamic tissue was immediately frozen at −80° C. A maximum of two offspring per dam were analysed to minimize litter-dependent bias. All studies were performed using male offspring. Microarray experiments of mice hypothalamic RNA were performed as single-color experiments using 4_44K Mouse (v2) Whole Genome Arrays from Agilent Technologies (Santa Clara, CA). First, differentially expressed genes between the CO group and HFD group, were identified using the Rank Product test. Genes were called significant with a percentage false positive below 0.001. All statistical calculations were performed using R version 3.1.2 and Bioconductor. Functional Annotation Clustering was performed by DAVID Bioinformatics Resources (http://david 6.7.abcc.ncifcrf.gov/home.jsp).