"Healthy" soybean oil causes genetic changes in the brain linked to neurological disease

"Healthy" soybean oil causes genetic changes in the brain linked to neurological disease

Eating soybean oil has already been linked to obesity and diabetes.[1] Now new research from scientists at the University of California Riverside shows it could also adversely affect neurological conditions like autism, Alzheimer’s disease, Parkinson's disease, anxiety, schizophrenia, and depression.[2]
The study also debunks advertising claims that the low-linoleic acid Plenish soybean, developed by DuPont Pioneer, has a "healthier nutritional profile" when "health" is viewed holistically.
Soybean oil is used for fast food frying, added to packaged foods, and fed to livestock. It is by far the most widely produced and consumed edible oil in the US, according to the US Department of Agriculture. The Plenish soybean is genetically engineered to have low linoleic acid, resulting in an oil that's claimed to be healthy because it generates less trans fats during cooking. Trans fats are linked with heart disease.
The new study, published this month in the journal Endocrinology, compared mice fed three different diets high in fat: "conventional" soybean oil (high in linoleic acid), Plenish soybean oil, and coconut oil. There was also an additional low-fat control diet.
The researchers don't define "conventional" soybean oil in their paper but it's almost certain that it's derived from GM Roundup Ready soybeans, as around 94% of the US soybean crop is of this type and the researchers don't describe in their paper what would be a complex process of sourcing oil from non-GMO beans. The corresponding author, Margarita Curras-Collazo, a UCR associate professor of neuroscience, did not respond to GMWatch's requests for clarification on this.
The researchers performed a transcriptomic analysis, a type of molecular analysis that looks at gene expression, on all three groups of animals.
They did not find any difference between the GM low-linoleic and "conventional" soybean oil’s effects on the brain. Specifically, the scientists found pronounced effects of the oil on the hypothalamus, where a number of critical processes take place.
The results showed that compared to the coconut oil and low-fat control diets, the two soybean oil-based diets resulted in a significant dysregulation of more than 100 hypothalamic genes, including those involved in neurochemical and neuroendocrine pathways and metabolic and neurological disorders.
“The hypothalamus regulates body weight via your metabolism, maintains body temperature, is critical for reproduction and physical growth as well as your response to stress,” said Margarita Curras-Collazo.
The team determined a number of genes in mice fed soybean oil were not functioning correctly. One such gene produces the “love” hormone, oxytocin. In soybean oil-fed mice, levels of oxytocin in the hypothalamus went down.
The research team believe that their discovery could have ramifications not just for energy metabolism, but also for proper brain function and diseases such as autism or Parkinson’s disease. However, it is important to note there is no proof the oil causes these diseases.
A separate study from UCR researchers found in 2015 that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice.[3] Then in a 2017 study, the same group learned that if soybean oil is genetically engineered to be low in linoleic acid, it induces less obesity and insulin resistance.[4]
With regard to the new study on brain effects, the research team has not yet isolated which chemicals in the oil are responsible for the changes they found in the hypothalamus. But they have ruled out two candidates. It is not linoleic acid, since the modified oil also produced genetic disruptions; nor is it stigmasterol, a cholesterol-like chemical found naturally in soybean oil.
Identifying the compounds responsible for the negative effects is an important area for the team’s future research.
“This could help design healthier dietary oils in the future,” said Poonamjot Deol, an assistant project scientist in Sladek’s laboratory and first author on the study.
“The dogma is that saturated fat is bad and unsaturated fat is good. Soybean oil is a polyunsaturated fat, but the idea that it’s good for you is just not proven,” Sladek said.
Indeed, coconut oil, which contains saturated fats, produced very few changes in the hypothalamic genes. GMWatch readers will note that there's no need to "design" healthier oils when naturally healthy oils already exist – coconut oil being a case in point.
“If there’s one message I want people to take away, it’s this: reduce consumption of soybean oil,” Deol said.
Additionally, the team notes the findings only apply to soybean oil — not to other soy products or to other vegetable oils.
“Do not throw out your tofu, soymilk, edamame, or soy sauce,” said Frances Sladek, a UCR toxicologist and professor of cell biology. “Many soy products only contain small amounts of the oil, and large amounts of healthful compounds such as essential fatty acids and proteins.”
GMWatch would add that if you eat soy products, it's vital to source organic and non-GMO soy, at the very least to avoid residues of the glyphosate that can be present at high levels in GM glyphosate-tolerant soy. GM soy has been found in animal feeding studies to produce adverse effects on the liver, pancreas and male testes. No one knows if this is due to the glyphosate residues, or some mutagenic effect of the GM process on the soy plants, or both.
Looking at the bigger picture, the new study has a lesson for those who enthuse about nutritionally enhanced GM foods. That is that a healthy nutritional profile should be defined holistically, not just by looking at one or a few nutrients. It is counter-productive to engineer a food that is meant to be heart-healthy if it is likely to damage brain function.
Notes
1. See:
* Costa CA, Carlos AS, dos Santos Ade S, Monteiro AM, Moura EG, Nascimento-Saba CC. Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil. Clinics 2011;66(10):1811–1816.
* Deol P, Fahrmann J, Yang J, Evans JR, Rizo A, Grapov D, Salemi M, Wanichthanarak K, Fiehn O, Phinney B, Hammock BD, Sladek FM. Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice. Sci. Rep. 2017;7(1):12488.
* Deol P, Evans JR, Dhahbi J, Chellappa K, Han DS, Spindler S, Sladek FM. Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: potential role for the liver. PLoS One 2015;10(7):e0132672. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132672
* Mamounis KJ, Yasrebi A, Roepke TA. Linoleic acid causes greater weight gain than saturated fat without hypothalamic inflammation in the male mouse. J. Nutr. Biochem. 2017;40:122–131.
2. Deol P et al. Dysregulation of hypothalamic gene expression and the oxytocinergic system by soybean oil diets in male mice. Endocrinology 2020:bqz044. https://doi.org/10.1210/endocr/bqz044
3. Deol P et al. Deol P, Evans JR, Dhahbi J, Chellappa K, Han DS, Spindler S, Sladek FM. Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: potential role for the liver. PLoS One 2015;10(7):e0132672. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132672
4. Deol P, Fahrmann J, Yang J, Evans JR, Rizo A, Grapov D, Salemi M, Wanichthanarak K, Fiehn O, Phinney B, Hammock BD, Sladek FM. Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice. Sci. Rep. 2017;7(1):12488.
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The new study:
Dysregulation of hypothalamic gene expression and the oxytocinergic system by soybean oil diets in male mice
Poonamjot Deol et al (2020)
Endocrinology, bqz044
Published: 08 January 2020
https://doi.org/10.1210/endocr/bqz044 (open access)
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-seq 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 two soybean oil diets had similar, albeit non-identical, 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 while 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 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 mRNA levels could be associated with the diabetic state. Given its ubiquitous presence in the American diet, the observed effects of soybean oil on hypothalamic gene expression could have important public health ramifications.

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