Department of Molecular, Cell and Systems Biology, University of California, Riverside, California.
Neuroscience Graduate Program, University of California, Riverside, California.
Endocrinology. 2020 Feb 1;161(2). doi: 10.1210/endocr/bqz044.
Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.
在过去的半个世纪中，大豆油的消费大大增加，与肥胖症和糖尿病有关。为了检验大豆油饮食会改变下丘脑基因表达并伴有代谢表型的假设，我们使用雄性小鼠进行了 RNA 测序分析，这些雄性小鼠喂食等热量的高脂肪饮食，这些饮食的基础是常规的大豆油（富含亚油酸，LA）、一种基因改良的低 LA 大豆油（Plenish）和椰子油（富含饱和脂肪，不含 LA）。这两种大豆油饮食对下丘脑转录组有相似但不完全相同的影响，而椰子油饮食与低脂对照饮食相比影响可以忽略不计。失调的基因与炎症、神经内分泌、神经化学和胰岛素信号有关。与两种对照饮食相比，只有 Oxt 是两种大豆油饮食上调的具有代谢、炎症和神经学相关性的唯一基因。与下丘脑室旁核和视上核的 oxytocin 免疫反应减少相比，血浆 oxytocin 和下丘脑 Oxt 增加。大豆油饮食的这些中枢和外周作用与葡萄糖不耐受有关，但与体重无关。在富含豆固醇（一种存在于大豆油中的植物固醇）的椰子油饮食中，没有观察到下丘脑 Oxt 和血浆 oxytocin 的改变。我们推测，无论是豆固醇还是 LA 都不是大豆油饮食对 oxytocin 产生影响的原因，并且 Oxt 信使 RNA 水平可能与糖尿病状态有关。鉴于大豆油在美国饮食中的普遍存在，其对下丘脑基因表达的观察到的影响可能具有重要的公共卫生意义。
