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

Question
Could soybean oil affect gene expression in the hypothalamus?
Takeaway
This 2020 mouse study indicates a diet rich in soybean oil, compared to a diet containing a similar amount of saturated fat, leads to changes in the expression of genes associated with inflammation, neuroendocrine function, and neurological signaling. These shifts suggest mechanisms by which soybean oil may have contributed to the rise in obesity and diabetes, given the dramatic increase in the oil’s consumption in the 20th century. Further research is needed to confirm the significance of these findings.

A growing body of evidence suggests polyunsaturated fats contribute to the obesity epidemic (1). Soybean oil consumption increased more than 1,000-fold in the U.S. in the 20th century, and consumption of linoleic acid has increased from less than 1% of total calories to 7.4% (2). Rat studies have indicated diets rich in soybean oil contribute to the development of obesity and diabetes.

This may be due to the effect of soybean oil on the hypothalamus, the region of the brain that regulates nutritional status and controls food intake, energy balance, and homeostasis (3). Previous research has shown alterations in dietary unsaturated fat intake modulate fatty acid levels in the brain, and with them, gene expression (4).

This study tested such hypothalamic effects, comparing the impact of four diets with differing amounts of linoleic acid and/or saturated vs. unsaturated fat. Mice were fed one of five diets: 1) a low-fat control diet, or 2) a diet with 40% of calories coming from coconut oil (saturated fat), 3) a mix of coconut and soybean oil (unsaturated fat), 4) a mix of coconut oil and a modified soybean oil containing no linoleic acid, or 5) coconut oil with added stigmasterol (ST). Comparing these diets allowed researchers to isolate the effects of all saturated fats, and linoleic oil specifically, on hypothalamic gene expression.

Diets high in soybean oil led to dysregulation of a variety of genes, as shown in the figure below. This included dysregulation of genes related to neuroendocrine processes, inflammation, and insulin and growth factor signaling. Researchers focused particularly on the effect of soybean oil on oxytocin (OXT) regulation.

Oxytocin plays an important role in the regulation of energy balance, body weight, and homeostasis (5). In this study, diets rich in soybean oil more than doubled plasma OXT levels relative to the coconut oil and control diets, with little variation occurring between the diets that differed only in their levels of linoleic acid. Notably, OXT is believed to regulate eating behavior and satiety, but these shifts were not correlated with any significant difference in food consumption between diets (6). Defective OXT signaling is also associated with a variety of neurological disorders, including depression, schizophrenia, and autism (7). This dysregulation, along with the dysregulation of other genes associated with schizophrenia, depression, anxiety, and Alzheimer’s disease on a diet rich in soybean oil, suggests the oil may have potential long-term impacts on mental health.

Given this was a gene regulation study in mice, these effects are extremely preliminary. In light of the dramatic increase in soybean oil consumption in the United States in the 20th century, however, and the ubiquity of soybean oil in the current American diet, even small deleterious effects will affect a large segment of the population. Further research is needed to explore the validity and clinical significance of these associations.

Notes

1. Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil; Omega-6 and omega-3 oxylipins are implicated in soybean-oil-induced obesity in mice; Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: Potential role for the liver; High-fat diet-induced hyperglycemia and obesity in mice: Differential effects of dietary oils; Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse; Intake of farmed Atlantic salmon fed soybean oil increases insulin resistance and hepatic lipid accumulation in mice
2. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century
3. Hypothalamic fatty acid sensing in the normal and diseased states; Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size
4. Modulation of brain PUFA content in different experimental models of mice; Changes in dietary fatty acids alter phospholipid fatty acid composition in selected regions of the rat brain; Central administration of oleic acid inhibits glucose production and food intake; Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression; Various dietary fats differentially change the gene expression of neuropeptides involved in body weight regulation in rats; Safflower (n-6) and flaxseed (n-3) high-fat diets differentially regulate hypothalamic fatty acid profiles, gene expression, and insulin signalling
5. The anorexigenic neural pathways of oxytocin and their clinical implication; A new horizon: Oxytocin as a novel therapeutic option for obesity and diabetes
6. Oxytocin and vasopressin systems in obesity and metabolic health: Mechanisms and perspectives
7. The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings; Differential correlations between plasma oxytocin and social cognitive capacity and bias in schizophrenia; intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism; Autism, oxytocin and interoception; The analgesic effects of oxytocin in the peripheral and central nervous system