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Mechanistic studies of long chain omega-3 fatty acid supplementation and inflammation in metabolic syndrome.

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Which omega 3 fatty acids tackle development of cardiovascular diseases

Obesity rates are increasing worldwide in parallel with the prevalence of metabolic syndrome (MetS), a chronic state of inflammation characterised by increased blood lipids and hypertension. EU-funded scientists have tested different omega 3 fatty acids on the arch enemy of cardiovascular health, chronic inflammation.

Health

Abdominal obesity, a large waistline, is a frequent cause of chronic inflammation, predisposing to MetS. The consequent unprecedented social and economic impacts on global health care burden are crying out for research dedicated to identifying effective strategies that prevent or decrease chronic inflammation among at-risk patients. Nutrients, in particular omega 3 fatty acids, play a key role in attenuating or sustaining chronic inflammation. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have raised tremendous interest due to their blood lipid lowering effect and purported anti inflammatory potential. However, almost all studies so far have used a mix of the two, and therefore their individual role has not been elucidated or compared yet.

EPA v DHA potency

Supported by the Marie Skłodowska-Curie programme, the PIMS project investigated whether DHA and EPA have similar or different effects on chronic inflammation, and if so, by which mechanisms. “The Lamarche lab previously showed that DHA is more potent than EPA in reducing some of the inflammation blood markers in adults,” recalls Benoît Lamarche, supervisor during the outgoing phase. “The impact of EPA vs. DHA supplementation on anti-inflammatory effects and any disparity caused by sex was investigated through the study of specific inflammation markers in the bloodstream, immune cells and abdominal adipose tissue,” explains Cécile Vors, postdoctoral fellow. The trial used a double-blind, crossover randomised, placebo-controlled design in men and women with MetS.

Results explaining anti-inflammatory effects of DHA and EPA

The main results achieved so far suggest that neither immune cells nor superficial abdominal adipose tissue play a significant role in explaining the difference between EPA and DHA in modulating chronic inflammation. However, the stronger anti-inflammatory effects of DHA compared with EPA may be due, in part, to changes in specific bioactive lipid mediators derived from DHA and EPA. Bioactive lipid mediators are involved in signalling, especially in inflammation resolution. Further data are awaited based on the in vivo tracking of key inflammatory proteins, such as C-reactive protein and serum amyloid A. The PIMS team expects imminent breakthroughs in explaining the anti-inflammatory effects of DHA and EPA.

Powerful analysis method caused a delay in results collation but future steps well on track

Ironically, previously developed new methods from the Lamarche lab using an innovative powerful proteomics approach to study in vivo lipoprotein metabolism were difficult to apply in PIMS research. Despite a significant delay over 2 years for such analytical developments, the enrichment data for the key inflammation proteins were finally available for modelling a few months ago. The good news is that this work is being finalised into an ongoing publication. Future research plans are looking very bright. Data from the unique ComparED clinical study will be further analysed and the results will be confirmed through publication in three high impact journals. The American Journal of Clinical Nutrition is targeted for publication of modelling data and Circulation Journal is expected to publish the data on bioactive lipid mediators) “Further potential collaborative work on prostaglandins – bioactive lipid molecules involved in oxidative stress – is imminent, and will nicely complement the results already obtained in the PIMS project,” adds the fellow. “I am truly indebted to the Marie Skłodowska-Curie Research Fellowship programme,” Cécile Vors emphasises. As well as acquisition of skills in adipose tissue and omega-3 metabolism and data modelling, she also plans to be a candidate for both American and European Young Scientist awards in 2021.

Keywords

PIMS, EPA, DHA, chronic inflammation, MetS, omega 3 fatty acids

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