High-Fat Diet and Memory Decline: Investigating the Role of Fatty Acids in Cellular Inflammation

Sunday - October 1 2023, 04:21 UTC - 1 year ago

A study from The Ohio State University in cell cultures and brain tissue from aging mice has found that high-fat foods may lead to memory decline. The omega-3 fatty acid DHA can shield the brain from the detrimental effects of an unhealthy diet by reducing fat-triggered inflammation at the cellular level. Palmitic acid, the most abundant saturated fatty acid in high-fat foods, may lead to inflammation in microglia and hippocampal neurons.

New research suggests several mechanisms through which high-fat foods may impact brain cells, potentially elucidating the association between a high-fat diet and memory decline, particularly in aging. A study from The Ohio State University conducted in cell cultures indicates that the omega-3 fatty acid DHA could shield the brain from the detrimental effects of an unhealthy diet by reducing fat-triggered inflammation at the cellular level. Separate experiments using brain tissue from aging mice showed a high-fat diet may lead specific brain cells to overdo cell-signaling management in a way that interferes with the creation of new memories. The same lab found in an earlier study in aging rats that a diet of highly processed ingredients led to a strong inflammatory response in the brain that was accompanied by behavioral signs of memory loss – and that DHA supplementation prevented those problems.

"The cool thing about this paper is that for the first time, we’re really starting to tease these things apart by cell type," said senior author Ruth Barrientos, an investigator in Ohio State’s Institute for Behavioral Medicine Research and associate professor of psychiatry and behavioral health and neuroscience in the College of Medicine.

"Our lab and others have often looked at the whole tissue of the hippocampus to observe the brain’s memory-related response to a high-fat diet. But we’ve been curious about which cell types are more or less affected by these saturated fatty acids, and this is our first foray into determining that." .

The study was published recently in the journal Frontiers in Cellular Neuroscience. For this work, the researchers focused on microglia, cells in the brain that promote inflammation, and hippocampal neurons, which are important for learning and memory. They used immortalized cells – copies of cells taken from animal tissue that are modified to continuously divide and respond only to lab-based stimulation, meaning their behavior may not precisely match that of primary cells of the same type.

Researchers exposed these model microglia and neurons to palmitic acid, the most abundant saturated fatty acid in high-fat foods like lard, shortening, meat, and dairy products, to observe how it affected gene activation in the cells as well as functioning of mitochondria, structures inside cells that have a primary metabolic role of generating energy. Results showed that palmitic acid prompted gene expression changes linked to an increase in inflammation in both microglia and neurons, though microglia had a wider range of affected inflammatory genes. Pre-treatment of these cells with a dose of DHA, one of two omega-3 fatty acids in fish and other seafood and available in supplement form, had a strong protective effect against the increased inflammation in both cell types.

"Previous work has shown that DHA is protective in the brain and that palmitic acid has been detrimental to brain cells, but this is the first time we’ve looked at how DHA can directly protect against the effects of palmitic acid in those microglia, and we see that there is a strong protective effect," said Michael Butler, first author of the research and a doctoral student in neuroscience at The Ohio State University.

The findings are important for understanding the consequences of a high-fat diet on the brain, as well as the potential preventative and protective effects of DHA, the researchers said.