Department of Biological Sciences, SUNY Old Westbury, Old Westbury, New York, USA.
Department of Biological Sciences, SUNY Old Westbury, Old Westbury, New York, USA.
J Nutr Biochem. 2022 Aug;106:109033. doi: 10.1016/j.jnutbio.2022.109033. Epub 2022 Apr 29.
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 is 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 the 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 to endocrine function signaling pathways CCKR and GnRH. Further examination of proliferation and migration shows low concentrations of oleic acid to stimulate proliferation and high concentrations of both oleic and palmitic acid to stimulate apoptosis. Oleic acid also reduces hypothalamic neuronal migration, with little effect from palmitic acid. The results show the two most abundant fatty acids in a high-fat diet impact hypothalamic neuronal proliferation and migration. The results also uncovered potential signaling pathways affected by oleic and palmitic acid and suggest one mechanism of prenatal high-fat diet-induced neurogenesis events may be through these two abundant fatty acids.
产前高脂肪饮食暴露会增加胚胎下丘脑的神经发生事件,并使后代容易肥胖。涉及这些神经发生饮食作用的分子机制尚不清楚。本研究调查了丰富于高脂肪饮食中的油酸和棕榈酸对下丘脑神经元转录组的影响,以及这些变化如何影响神经发生事件。结果表明,低浓度和高浓度的油酸或棕榈酸处理对差异基因转录有不同的影响。基因本体分析揭示了几个涉及基因调控和蛋白质产生的细胞途径中的显著基因富集,特别是增殖、迁移和细胞存活。丰富的信号通路包括 Wnt、整合素、PDGF 和细胞凋亡,以及内分泌功能信号通路 CCKR 和 GnRH。对增殖和迁移的进一步研究表明,低浓度的油酸刺激增殖,高浓度的油酸和棕榈酸刺激凋亡。油酸还减少了下丘脑神经元的迁移,而棕榈酸的影响很小。研究结果表明,高脂肪饮食中两种最丰富的脂肪酸会影响下丘脑神经元的增殖和迁移。研究结果还揭示了油酸和棕榈酸影响的潜在信号通路,并表明产前高脂肪饮食诱导的神经发生事件的一种机制可能是通过这两种丰富的脂肪酸。