Levels of Fatty Acid Low in MS Patients, Likely Affecting Immune System

Oleic acid, a type of fatty acid, is important for the function of immune cells that are dysregulated in multiple sclerosis (MS), an early study shows.

A diet rich in oleic acid may potentially be beneficial for these patients, although researchers emphasized the need for more studies.

The study, “Oleic acid restores suppressive defects in tissue-resident FOXP3 Tregs from patients with multiple sclerosis,” was published in The Journal of Clinical Investigation.

Regulatory T-cells (Tregs), a type of immune cell, help to regulate the activity of the immune system. Tregs normally help prevent other immune cells from attacking healthy tissue. But in MS, the immune system does attack healthy tissue — specifically the nervous system — and this has been linked to abnormal Treg function.

Immune cells like Tregs require a substantial amount of energy to carry out their cellular activities. Unlike many other types of cells, which get energy predominantly by metabolizing sugar molecules (glucose), Tregs are more reliant on fatty acid metabolism for energy.

A team led by researchers at Yale University investigated if fatty acids in the body could help drive Treg to work as intended.

Researchers first conducted a series of biochemical tests on Tregs taken from healthy human adipose (fat) tissue. These analyses revealed that Tregs are largely reliant on a specific fatty acid called oleic acid, which is one of the most abundant fatty acids in the human body.

Exposure to oleic acid caused the cells to become more metabolically active, and led to increased expression of genes associated with Treg function, indicating that oleic acid helped to trigger Tregs’ immune-suppressing activity. In contrast, another fatty acid called arachidonic acid — which is known to have pro-inflammatory effects — reduced Treg activity.

Next, they analyzed Tregs isolated from fat tissue of eight MS patients and eight healthy controls. Two of these patients had not receive treatment for more than 1.5 years at the time their cells were collected, whereas the other six had not been treated for at least six months.

Data showed that Tregs from healthy individuals were more similar to oleic acid-treated Tregs from the earlier experiments in terms of gene expression profile than were Tregs from MS patients. Notably, the differences were more pronounced in the two patients untreated for about 1.5 years.

According to the researchers, this result indicates that immune-targeting treatments may help to normalize Treg function in MS patients.

Further analyses showed that Tregs from MS patients generally had lower expression of genes that are activated by oleic acid exposure.

“These data suggest that Tregs in the blood and adipose tissue of healthy donors may be exposed to a lipid milieu that contains larger amounts of oleic acid than can be found in patients with MS,” the researchers wrote.

Consistent with this idea, the amount of oleic acid in fat tissue from MS patients was “strikingly reduced” compared to levels found in healthy controls. Furthermore, exposing Tregs from MS patients to oleic acid caused these cells to become more active, similarly to the previous experiments done using cells from healthy donors.

“We show that oleic acid partially restored defects in the suppressive function of Tregs isolated from patients with MS, which further suggests the importance of fatty acid species in counteracting inflammatory signals in the tissue,” the team wrote.

Since a person’s diet is one of the most important factors controlling how much oleic acid is in the body, the results indicate that diet may impact the development of MS.

“We’ve known for a while that both genetics and the environment play a role in the development of MS. This paper suggests that one of environmental factors involved is diet,” David Hafler, MD, study co-author and professor at Yale, said in a press release.

Importantly, the researchers stressed that the findings do not directly demonstrate that dietary differences are a cause of MS, or that consuming more oleic acid could be beneficial for MS patients.

According to the team, further studies are needed to better understand the relationship between fatty acids regulation in relation to the risk of autoimmune diseases and their impact on them.