Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice

Abstract

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.

Low‐Dose Coconut Oil Supplementation Induces Hypothalamic Inflammation, Behavioral Dysfunction, and Metabolic Damage in Healthy Mice

“…[33] In the present study, SO100 group was glucose intolerant after the supplementation period, while CO consumption did not affect glucose homeostasis. Studies have shown that SO has more diabetogenic effect than CO. [34][35][36] This is due to the difference in the composition of these oils (Table 1), CO is rich in saturated MCFA and SO has a high level of oleic acid, linoleic acid, and linolenic acid, [31] which can directly impact the dysregulation of gene expression in mice hypothalamus, such as gene coding for oxytocin, [34] which in turn plays an important role in glucose homeostasis. [37] In addition, we investigated obesity-related biomolecular markers, such as activation of inflammatory pathways and expression of the cytokines and chemokines in the epididymal adipose tissue, hypothalamus, and liver.…”

Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats

“…A recent study by Deol et al. demonstrated a profound dysregulation of hypothalamic gene expression in mice fed soy oil-containing diet compared to control and coconut oil-containing diet with different proportions of fatty acid composition ( Deol et al., 2020 ). An increase in oxytocin expression and a decrease of oxytocin immunoreactivity were detected in the hypothalamus of mice fed diet containing soybean oil compared to mice fed control or coconut oil-containing diet, clearly demonstrating that quality of fat consumption impacts on brain neurochemistry.…”

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

“…The Arg8-vasopressin kit has a sensitivity of 0.9 pg/mL in a dynamic range of 1.638–1,000 pg/mL. For the Enzo Life Sciences kits, samples underwent solid phase extraction using 200 mg C18 Sep-pak columns as previously described (Deol et al 2020 ). Plasma oxytocin and arginine vasopressin were quantified by interpolating absorbance or luminosity values, respectively, using a 4-parameter-logarithmic standard curve (MyAssays).…”