Do you need another alibi to daydream about travelling to Italy? Pompura et al. have given you the perfect ammunition. In short, they demonstrated that eating more olive oil might have a restorative effect on a crucial immune cell type in MS.
In the immune system, there are several types of T cells. One subtype that is potentially important in MS pathophysiology are the regulatory T cells also known as Tregs. These cells have essentially a suppressor function and need to keep all other immune cells in line. In cancer, an excess of Treg activity can prevent the immune system from destroying cancer cells. In autoimmune diseases, a deficiency of Treg activity can allow other immune cells to attack the brain and spinal cord.
Pompura et al. have shown that Tregs present in adipose tissue of pwMS are less regulatory than in healthy controls, and the reduced regulatory function was linked to a deficiency in “oleic acid”. Oleic acid is a mono-unsaturated omega-9 fatty acid that is ubiquitously present in olive oil (up to 80% of olive oil fat) and avocado. When Tregs are exposed to oleic acid, they tend to switch their metabolism from glucose consumption towards fatty acid oxidation, and in turn, this stimulates expression of FoxP3 which is the key cell surface marker of Tregs driving their suppressive potential. In the adipose tissue of pwMS, the researchers found lesser quantities of oleic acid leading them to hypothesise and demonstrate that co-culturing or ‘supplementing’ Tregs with oleic acid restored the suppressive Treg function in vitro (read: in a Petri dish).
Before you all head out to the store buying cartloads of extra-virgin olive oil, the following reflections:
- Adipose tissue? I thought MS was a brain disease.
Over the preceding years, it has become progressively more clear that childhood obesity is a risk factor to develop MS later on. If your BMI is above 30 kg/m2 at 18 years old, your risk of developing MS doubles. However, the underlying mechanism is unclear. One explanation centers around the fact that in obese individuals altered adipokine levels are found resulting in higher levels of low-grade inflammation. This pro-inflammatory activated immune state makes it (potentially) more likely to mistakenly attack myelin in the brain. Alternatively, high body mass index has been associated with low bio-availability of vitamin D which is another established risk factor for MS. Alternatively, obesity dysregulates gut microbiota favouring – again – a pro-inflammatory immune response. Alternatively, there is an unfavourable interaction with the most important genetic risk factor of MS. Participants who carried the high-risk HLA-DRB1*15 gene, did not carry the protective HLA-A*02 gene, and had a BMI of 27 kg/m2 or greater at age 20 had an OR of 16.2 for developing later MS, compared with those who had none of those risk factors. In contrast, subjects who had the same HLA profile but had not been obese at age 20 had an OR of 5.1.
Overall, the underpinnings of the obesity and MS link are unclear and, by extension, also the link between adipose Tregs and MS.
- Olive oil? I’m buying omega-3 at Holland & Barrett
The researchers added oleic acid to Tregs in an experimental setting, and this boosted their suppressive potential. In real-life, we ingest oleic acid indirectly when for example eating olive oil, and oleic acid circulates in plasma bound to triglycerides. It is unknown to what extent ingested oleic acid is proportional to the concentrations of oleic acid in plasma or adipose tissue, and whether higher intake results in influencing Tregs in vivo. Moreover, if this would be a very important strong effect, we would expect lower incidence of MS in people around the Mediterranean which is – Sardinia, Sardinia, Sardinia – not the case. Furthermore, results from studies aimed at supplementing polyunsaturated fatty acids have been disappointing. Omega‐6 fatty acids (11 to 23 g/day linoleic acid) didn’t show any benefit in 144 pwMS. Linoleic acid (2.9 to 3.4 g/day) had no benefit in 65 chronic progressive pwMS. Omega‐3 fatty acids had no benefit in 292 relapsing remitting pwMS.
In summary, we know already for more than 50 years that the Mediterranean diet has been linked to lower rates of coronary artery disease, and many people believe this is due to the abundance of olive oil in the diet. However, after all these years it is still unclear whether the diet effect is “transferable” to populations living far from the Mediterranean region such as for example the UK. The question remains to what extent the Mediterranean diet is an expression of culture, history and lifestyle. Some have argued that the relaxing psychosocial environment, mild climatic conditions, preservation of the extended-family structure, and even the afternoon siesta habit in the Mediterranean region may play contributory roles. The same rationale applies to oleic acid in pwMS. This study focuses on a micro-function of fatty acids in the adipose tissue of humans with one specific autoimmune disease, and found an association between oleic acid and suppressive function of adipose Tregs. The bigger picture is totally unclear, and especially whether an oleic-rich diet would impact on MS disease and how. Nonetheless, we do know that diets high in oleic acid may beneficially modify body composition and regional fat distribution which is undeniably – bathing suit, bathing suit, bathing suit – a good thing.
Pompura SL, Wagner A, Kitz A, LaPerche J, Yosef N, Dominguez-Villar M, Hafler DA
FOXP3+ Tregs rely on fatty acid β-oxidation-driven (FAO-driven) oxidative phosphorylation (OXPHOS) for differentiation and function. Recent data demonstrate a role for Tregs in the maintenance of tissue homeostasis, with tissue-resident Tregs possessing tissue-specific transcriptomes. However, specific signals that establish tissue-resident Treg programs remain largely unknown. Tregs metabolically rely on FAO, and considering the lipid-rich environments of tissues, we hypothesized that environmental lipids drive Treg homeostasis. First, using human adipose tissue to model tissue residency, we identified oleic acid as the most prevalent free fatty acid. Mechanistically, oleic acid amplified Treg FAO-driven OXPHOS metabolism, creating a positive feedback mechanism that increased the expression of FOXP3 and phosphorylation of STAT5, which enhanced Treg-suppressive function. Comparing the transcriptomic program induced by oleic acid with proinflammatory arachidonic acid, we found that Tregs sorted from peripheral blood and adipose tissue of healthy donors transcriptomically resembled the Tregs treated in vitro with oleic acid, whereas Tregs from patients with multiple sclerosis (MS) more closely resembled an arachidonic acid transcriptomic profile. Finally, we found that oleic acid concentrations were reduced in patients with MS and that exposure of MS Tregs to oleic acid restored defects in their suppressive function. These data demonstrate the importance of fatty acids in regulating tissue inflammatory signals.