Increasing fatty acid levels may restore immune response in MS
A new study examined diet and immune response, comparing healthy individuals with those living with multiple sclerosis (MS).
The researchers found that the people with MS had low levels of oleic acid, which may have led to autoimmunity and inflammation.
MS is an autoimmune condition that targets healthy tissue within the central nervous system. Symptoms include fatigue, vision loss, and muscle weakness.
Although the exact causes are unknown, research indicates that environmental factors, such as diet, play a crucial role in regulating this immune response.
Scientists at the Yale School of Medicine in New Haven, CT, have published a study in The Journal of Clinical Investigation that examined the effect of fatty acids, specifically oleic acid, on immune regulatory signals.
They found that people with MS had reduced levels of oleic acid in fat tissue aspirate and that replenishing the tissue with oleic acid may partially restore certain immune functions.
Fatty acids are important building blocks that serve as an energy source within the body. They are commonly present in high fat foods, such as vegetable oils, nuts, and meats.
Oleic acid is one of the most prevalent fatty acids in human and animal fat tissues. Research has implicated it as a key component of signaling for immune cells residing in fat tissues.
To better understand the effects of oleic acid, the scientists focused on a set of cells in the immune system known as regulatory T cells (Tregs). Tregs are responsible for mediating the body’s immune response by suppressing other cells and preventing autoimmunity.
Previous research has demonstrated that people with autoimmune conditions have defective Treg functions.
Treg activation primarily relies on two metabolic pathways: fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS). Increased activation of this combined pathway enhances certain Treg-related genes, notably FOXP3, which allows the cells to produce a suppressive immune response.
Fatty acids commonly follow these same two pathways during digestion. Considering this overlap in pathways, the researchers hypothesized that fatty acids are necessary to drive the suppressive function of Tregs.
For all parts of the study, the researchers conducted experiments in the laboratory by isolating Tregs from human blood and fat tissue and treating them with specific fatty acids.
First, the researchers examined changes in both the pathway and Treg-related genes by adding oleic acid to Tregs from healthy individuals.
The presence of oleic acid led to increased activation of the FAO-driven OXPHOS pathway. Tregs also showed increased expression and stability of the FOXP3 gene, though this increase reached a maximum level after 72 hours.
These findings indicate that oleic acid serves as a metabolic signal to promote FAO-driven OXPHOS, which, in turn, promotes the FOXP3 gene, which then finally activates the Tregs.
To check whether or not this occurred across all fatty acids, the team followed the same procedure for several different fatty acids. Oleic acid was unique in increasing FOXP3 expression.
The study also compared the effects of oleic acid with those of arachidonic acid, which is another fatty acid known to alter T cell function to induce an inflammatory response.
The researchers treated Tregs with either oleic acid or arachidonic acid and observed that both groups expressed unique gene signatures.
Oleic acid-treated Tregs displayed an enhancement of genes involved in the FAO pathway. On the other hand, arachidonic acid-treated Tregs displayed an enhancement of a contrasting set of genes involved in inflammation.
These Tregs demonstrated an inverse relationship between the two fatty acids. Many of the genes that were enhanced in the oleic acid-treated Tregs were the same ones that were suppressed in the arachidonic acid-treated Tregs.
A potential explanation for these results is that Tregs are able to adapt to environmental signals to carry out the appropriate immune responses.
Next, the team expanded on these results by comparing the gene signatures of Tregs from healthy individuals and people with MS.
Tregs from healthy individuals most closely resembled the gene signature that oleic acid induced, while Tregs from people with MS resembled the gene signature that arachidonic acid induced.
From these findings, the researchers inferred that people with MS have lower oleic acid levels and higher arachidonic acid levels.
As a result, these MS Tregs lose their suppressive function, and inflammation ensues. These Treg defects then cause the body to attack healthy cells and undergo inflammation. These are both traits linked to MS.
The researchers attempted to reverse this defect by exposing the MS Tregs to oleic acid. Once exposed, these Tregs displayed the gene signature present in healthy individuals, indicating that normal levels of oleic acid partially restored Treg-suppressive function.
Additionally, this suggests that oleic acid may act against inflammatory cues driven by arachidonic acid.
It is important to note that these findings are not generalizable to all people with MS. This is due to the higher average age and body mass index (BMI) of the study participants relative to those of the healthy individuals.
Further research is necessary to determine whether or not an oleic acid-rich diet is a beneficial treatment for MS.
However, this study provides evidence that fatty acids are important in maintaining a balance in MS-related functions of the immune system.