Prenatal high-fat diet exposure increases hypothalamic neurogenesis events in embryos and programs offspring to be obesity-prone. The molecular mechanism involved in these dietary effects of neurogenesis are unknown. This study investigated the effects of oleic and palmitic acids, which are abundant in a high-fat diet, on the hypothalamic neuronal transcriptome and how these changes impact neurogenesis events. The results show differential effects of low and high concentrations of oleic or palmitic acid treatment on differential gene transcription. Gene ontology analysis uncovered significant gene enrichment in several cellular pathways involved in gene regulation and protein production, particularly with proliferation, migration, and cell survival. The enriched signaling pathways include Wnt, integrin, PDGF, and apoptosis, in addition endocrine function signaling pathways CCKR and GnRH. Further examination of proliferation and migration show low concentrations of oleic acid to stimulate proliferation and high concentrations of both oleic and palmitic acid to stimulate apoptosis. Oleic acid also reduced hypothalamic neuronal migration, with little effects by palmitic acid. The results show direct impact of the two most abundant fatty acids in a high fat diet to directly impact hypothalamic neuronal proliferation and migration. The results also uncovered signaling pathways affected by oleic and palmitic acid and suggest a mechanism of prenatal high-fat diet induced neurogenesis events is through these two abundant fatty acids.

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Concentration-dependent change in hypothalamic neuronal transcriptome by the dietary fatty acids: oleic and palmitic acids