Leukocytes from obese individuals exhibit an impaired SPM signature

What is it about?

Our study describes an unbalanced production of SPM with respect to pro-inflammatory lipid mediators such as leukotriene B4 and prostaglandins in peripheral leukocytes isolated from individuals with morbid obesity. In our study, we also performed mechanistic studies assessing different aspects of SPM biosynthesis, in particular implicated in the formation of resolvins of the D series from DHA (i.e. membrane fatty acid transporter MFSD2A and 15-LOX and 5-LOX enzymes). The results obtained support the concept that reduced 15-LOX activity, rather than reduced DHA uptake, could be the cause of impaired D-series resolvin production in obese leukocytes. Moreover, we identified decreased 5-LOX levels together, reduced 5-LOX Ser271 phosphorylation and distinct intracellular 5-LOX redistribution in leukocytes from obese individuals. However, these alterations in the 5-LOX enzyme appeared to not be critical, since the formation of D-series resolvins was rescued by incubation with the intermediate precursor 17-HDHA. Together our findings provide data confirming the impaired production of pro-resolving mediators in human obesity and suggest that administration of intermediate precursors of SPM biosynthesis (i.e. 17-HDHA) could be more efficient in overriding impaired formation of these pro-resolving lipid mediators in conditions characterized by dysfunctional LOX activity, such as obesity.

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