1-O-alkyl-glycerols from squid Berryteuthis magister reduce inflammation and modify fatty acid and plasmalogen metabolism in asthma associated with obesity

Denisenko Y, Novgorodtseva T, Antonyuk M, Yurenko A, Gvozdenko T, Kasyanov S, Ermolenko E, and Sultanov R. (2023) 1-O-alkyl-glycerols from squid Berryteuthis magister reduce inflammation and modify fatty acid and plasmalogen metabolism in asthma associated with obesity. Marine Drugs

Asthma is a chronic disease of the lungs and is characterized by a narrowing of the airways due to inflammation or constriction, resulting in shortness of breath, wheezing, and coughing. One risk factor of asthma is obesity, and this can influence the incidence and presentation of the disease. A specific type of diagnosis is asthma associated with obesity, which is a more severe phenotype and is not easy to control and is often less responsive to typical asthma medication. The link between the two is thought to be chronic system inflammation because immunology studies have demonstrated that many inflammatory cells and mediators are involved in both asthma and obesity. The variety of immune mechanisms involved in asthma in people with obesity is what causes the challenges with treating and controlling the disease. The inability of using standard asthma care in obesity means there is a need for a more effective medication that can control the function of the immune and lung systemsin these individuals. Plasmalogens are a unique class of lipid that have important roles in the physiology of lungs and a reduction in plasmalogens is associated with asthma and chronic obstructive pulmonary disease (COPD). Plasmalogens are a large part of lung surfactant and may protect lungs from reactive oxygen species since they have antioxidant properties. Because of these roles, Denisenko et al suggest that a plasmalogen precursor, 1-O-alkyl-glycerols (AGs), may be a better treatment method for people with asthma and obesity.

In this study AGs were extracted from the digestive gland of the squid, Berryteuthis magister. There were 35 participants in the study, of which 19 (nine males and ten females) were obese and had asthma and 16 (7 males and 9 females) were healthy individuals to use as a control group. All underwent clinical, biochemical, and immunological exams to determine baseline levels before supplementation with AGs started. When analyzing plasmalogen levels, a reduction was seen in plasma of participants with asthma and obesity compared to the control group.

To determine whether AGs can effectively improve the lung function of people with asthma and obesity, the participants were supplemented with 0.4 g per day of AGs for three months and pulmonary function was measured looking at vital capacity, forced vital capacity, and forced expiratory volume in the first second. After one month and three months they found that AGs supplementation improved pulmonary function shown through increased forced vital capacity in the first second. As well, the obese asthmatic group had an increase in the ratio of forced vital capacity in the first second and vital lung capacity after both one month and three months of supplementation. In addition, plasmalogen level was also analyzed following the supplementation and was shown to increase after one and three months.

People with asthma and obesity are known to have chronic inflammation with a high generation of inflammatory cytokines including IL-6, TNF-α, IL-17, IL-1βγ. This study confirmed that the participants with asthma and obesity have increased inflammatory cytokine levels such as TNF-α, IL-2, IL-4, and IL-17a. After one month of supplementation with AGs TNF-α, IL-4, and IL-17a were decreased, however no differences were seen in IL-2, IL-6, IL-10, or IFN-γ. By the end of three months of supplementation IL-2, IL-4, IL-17a, and TNF-α were decreased, suggesting that long-term use of AGs has an anti-inflammatory effect in people with asthma and obesity.

Denisenko et al were interested in determining whether a plasmalogen precursor, 1-O-alkyl-glycerols, could act as an asthma treatment for people with asthma and obesity. Since both diseases are associated with high levels of inflammation, standard asthma treatments are often ineffective in people with obesity. Plasmalogens are known anti-oxidants and have anti-inflammatory capabilities, therefore supplementation with plasmalogens or a product that could raise plasmalogen levels, which are known to be reduced in both diseases, was theorized to be more effective than the typical asthma treatments. The authors demonstrated that even supplementation for one month began improving lung function and reducing inflammatory cytokines, and this was further improved by three months of supplementation with 0.4 g of AGs. Limitations of this work are that the sample size was quite small so looking at a larger population of both the people with asthma and obesity and the healthy controls could alter the trends seen. Going forward it would be interesting to determine if any of the changes seen in plasmalogen levels are driven by specific species and if so, whether supplementation or treatment with that species would show greater improvements.