High-Fat Diets Affect Genes Linked To Health Conditions Other Than Obesity

This study is unusual in its scope, feeding mice three different diets for 24 weeks where at least 40% of the calories came from fat, then they looked at the microbiome and genetic changes in all four parts of the intestine to study the many impacts of high-fat diets. One group of mice ate a diet based on saturated fat from coconut oil, another group ate a diet based on monounsaturated-modified soybean oil, and the third group ate a diet based on unmodified soybean oil rich in polyunsaturated fats. According to the researchers, Compared to a low-fat control diet group, all three groups experienced alarming changes in gene expression, the process that trunks genetic information into functional products, such as a protein. 

The researcher found intestinal changes such as major changes in genes related to fat metabolism and composition of gut bacteria like increases in pathogenic E. coli and suppression of Bacteroides that help to protect the body against pathogens. This study revealed that the expression of several neurotransmitter genes was changed by the high-fat diets, reinforcing the belief that the gut-brain axis can be impacted by diet. 

Other observations were more surprising, such as changes in genes regulating susceptibility to infectious diseases. “We saw pattern recognition genes, ones that recognize infectious bacteria, take a hit. We saw cytokine signaling genes take a hit, which helps the body control inflammation,” Sladek said. ‘So, it’s a double whammy. These diets impair immune system genes in the host, and they also create an environment in which harmful gut bacteria can thrive.”

The researchers' previous work with soybean oil demonstrated a link to obesity and diabetes; this paper shows that all three high-fat diets increase the expression of ACE2 and other host proteins that are used by spike protein to enter the body. Additionally, the high-fat diets increased signs of stem cells in the colon, which can be precursors to cancer. 

The coconut oil diet showed the greatest number of changes in terms of effects on gene expression, which was followed by the unmodified soybean diet. The researchers noted that the differences between the soybean diets suggest that polyunsaturated fatty acids in unmodified soybean oil, primarily linoleic acid, played a role in altering gene expression. 

Negative microbiome changes were also more pronounced in the soybean diet, which was also demonstrated by the researchers in previous work finding that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in 2015. The researchers went on to demonstrate that the oil could affect genes in the brain related to conditions such as anxiety, depression, autism, and Alzheimer’s disease in 2020. 

“There are some really good things about soybeans. But too much of that oil is just not good for you,” said UCR microbiologist Poonamjot Deol, who was co-first author of the current study along with UCR postdoctoral researcher Jose Martinez-Lomeli.

It was noted that the findings apply to soybean oil and not to other soybean products, tofu, or soybeans themselves. Although this study was in mice, humans share 97.5% of their working DNA, making the findings concerning as soybean oil is the most commonly consumed oil in America and it is being used increasingly more commonly around the globe.

Americans typically get 40% of their calories from fat which was mirrored in this study. However, one should not panic about a single meal, the long-term use is what causes the observed changes. The 24-week period is the equivalent of starting in humans from childhood through to middle age. The researchers hope that these findings will prompt people to examine their eating habits more closely.

“Some fat is necessary in the diet, perhaps 10 to 15%. Most people though, at least in this country, are getting at least three times the amount that they need,” Deol said. “One night of indulgence is not what these mice ate. It’s more like a lifetime of the food,” Deol added. 

“Some people think, ‘Oh, I’ll just exercise more and be okay. But regularly eating this way could be impacting your immune system and how your brain functions,” Deol said. “You may not be able to just exercise away these effects.”