SUN-101 Dysregulation of Hypothalamic Gene Expression by Soybean Oil Diets in Mice

Soybean oil is a major component of the American diet and its increased consumption correlates positively with the prevalence of obesity and diabetes in the U.S. Our previous findings showed that a high fat diet (HFD) enriched in soybean oil, similar to the American diet, induces more obesity, diabetes, insulin resistance and fatty liver in male mice than an isocaloric diet consisting of coconut oil (CO), as well as a substantial dysregulation of liver gene expression (PMID:28970503, 26200659). Here, RNA-seq analysis reveals that HFDs based on conventional soybean oil (SO), which is high in linoleic acid (LA), and a genetically modified, low-LA soybean oil called Plenish, have similar, albeit non identical, effects on hypothalamic gene expression; in contrast, a CO HFD has a negligible effect compared to the low fat vivarium chow (Viv) diet. Genes related to inflammation and oxidative stress, metabolism, obesity and diabetes, as well as those linked to neurological disorders, are dysregulated by SO and Plenish. Oxt, which encodes the neuropeptide oxytocin (OXT), is the only gene with metabolic and neurological significance upregulated by both soybean oil diets, but not CO, suggesting that Oxt gene expression is altered by neither LA nor the saturated fatty acids present in CO. In contrast, immunohistochemistry (IHC) shows that the two soybean oil diets reduce oxytocin protein (OXT) levels in the supraoptic and paraventricular nuclei of the hypothalamus, while OXT peptide levels are increased in the circulating blood, suggesting that a decrease in hypothalamic OXT may be responsible for SO-induced obesity and diabetes. The phytosterol stigmasterol found in both the SO and Plenish diets did not induce either obesity or diabetes nor affect the oxytocin pathway, suggesting that a component in soybean oil other than LA or stigmasterol is responsible for its metabolic effects. Given the impact that Oxt can have on metabolic processes as well as developmental disorders of social behavior including autism, depression and schizophrenia, the American diet based largely on soybean oil may have a broader impact on human health than previously appreciated.(Funding: NIH NIDDK, NIEHS T32, CCFA, Seed Grant-UCR).