Palmitic acid (PA) is one of the most common lipids found in breast milk, meat and dairy products. In a new study, researchers from the University of Toronto, Canada, found that when dietary levels of palmitic acid are low, it is made by the liver and transported to the developing brain. The results of this preclinical study emphasize the importance of palmitic acid for brain health and point to the need for more research on lowering palmitic acid levels in infant formulas. The results of the study were published online January 17, 2024, in Nature Communications under the title"Upregulated hepatic lipogenesis from dietary sugars in response to low palmitate feeding supplies brain palmitate".
Richard Bazinet of the University of Toronto, corresponding author of the paper, said, "When we changed the amount of palmitic acid in the diets of developing mice, there was no effect on the brain. These findings are surprising because when dietary lipids are lowered, lipids in the brain are usually lowered as well. But in this new study, the liver was able to increase lipid production to ensure that the brain got enough lipids, despite the great variation in dietary intake."
Palmitic acid is a saturated fat that supports brain health in a number of ways throughout a mammal's life. It contributes to the structure and function of myelin, the sheath that insulates nerve connections, and is a precursor to molecules that regulate inflammation and promote cell signaling.
Scientists have long known that humans and other mammals can obtain palmitic acid from food and also produce it in a process called de novo lipogenesis, which primarily requires glucose to synthesize palmitic acid. Little is known about which sources the body relies on at different stages of growth and maturation.
Bazinet said their findings highlight the importance of palmitic acid for brain health at all stages, especially during the developmental stages when the need for this fat is greatest.
Bazinet said, "Interestingly, while the brain makes palmitic acid, the liver does a lot of up-regulation of it. Redundancy in these systems is built in, so the body doesn't risk getting insufficient amounts of the nutrient."
Mackenzie Smith, first author of the paper and a doctoral student in Bazinet's lab, said the results should give pause to producers looking to reduce the amount of palmitic acid in infant formula.
Smith said, "We have the potential to reduce the amount of palmitic acid in formula, which could have a positive ecological impact, but we don't yet know the potential health effects. When the liver produces so much of the substance, could there be behavioral or developmental effects? Could there be negative effects on the liver?"
Image from Nature Communications, 2024, doi:10.1038/s41467-023-44388-4
Smith also noted that even mice that consumed the lowest amounts of palmitic acid through their diets still consumed higher levels of this lipid than some formula manufacturers are aiming for, Smith said, adding that this discrepancy adds to the rationale for further preclinical and human studies.
To reveal the source of palmitic acid in the brains of developing mice, these authors used a new carbon isotope technique. Isotopes are different versions of the same chemical element that have slightly different qualities; in this new study, they took advantage of natural differences in carbon isotope ratios in the environment, based on the way plants absorb carbon during photosynthesis.
Smith says, "Most plants use the same pathway to fix carbon from the atmosphere and have the same carbon isotope ratios, but sugars such as corn and sugarcane - which the liver uses to produce palmitic acid - have different carbon isotope ratios."
In the brains of mice, Smith said, features with reduced carbon isotope ratios indicate that palmitic acid is derived from food, while features with elevated carbon isotope ratios indicate that fat is synthesized from scratch.
These authors were able to track these features at multiple stages of mouse development, which led them to identify the liver as the primary source of palmitic acid in the developing brain of mice-a finding they confirmed by examining changes in genetics.
This approach opens up new research opportunities, Smith says, "Compared to traditional radiotracers, which are very expensive, this new technique allows for cost-effective, long-term study designs."
Researchers in Bazinet's lab are currently applying the same technique to adult brain tissue to build on current findings.Bazinet says this approach may provide a new way to measure and track the dietary sources of other lipid molecules and nutrients.
Bazinet said, "These issues may be flagged by this technique, such as tracking the source and amount of added sugars. This could be very beneficial to nutritional science."
