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Behçet’s disease (BD) is a relapsing, multisystem and inflammatory condition characterized by systemic vasculitis of small and large vessels. Although the etiopathogenesis of BD remains unknown, immune-mediated mechanisms play a major role in the development of the disease. BD patients present leukocyte infiltration in the mucocutaneous lesions as well as neutrophil hyperactivation. In contrast to neutrophils, whose involvement in the pathogenesis of BD has been extensively studied, the biology of monocytes during BD is less well known. In this study, we analyzed the phenotype and function of circulating monocytes of 38 BD patients from Hospital of Braga. In addition, we evaluated the impact of inflammatory and metabolomic plasma environment on monocyte biology. We observed a worsening of mitochondrial function, with lower mitochondrial mass and increased ROS production, on circulating monocytes of BD patients. Incubation of monocytes from healthy donors with the plasma of BD patients mimicked the observed phenotype, strongly suggesting the involvement of serum mediators. BD patients, regardless of their symptoms, had higher serum pro-inflammatory TNF-α and IP-10 levels and IL-1β/IL-1RA ratio. Untargeted metabolomic analysis identified a dysregulation of glycerophospholipid metabolism on BD patients, where a significant reduction of phospholipids was observed concomitantly with an increase of lysophospholipids and fatty acids. These observations converged to an enhanced phospholipase A2 (PLA 2 ) activation. Indeed, inhibition of PLA 2 with dexamethasone or the downstream cyclooxygenase (COX) enzyme with ibuprofen was able to significantly revert the mitochondrial dysfunction observed on monocytes of BD patients. Our results show that the plasma inflammatory environment coupled with a dysregulation of glycerophospholipid metabolism in BD patients contribute to a dysfunction of circulating monocytes.

Diacetyl is a flavoring that imparts a buttery flavor to foods, but the use or exposure to diacetyl has been related to some diseases. We investigated the effect of oral intake of diacetyl in male and female C57/Bl mice. We performed a target metabolomics assay using ultraperformance liquid chromatography paired with triple quadrupole mass spectrometry (UPLC-MS/MS) for the determination and quantification of plasmatic metabolites. We observed alterations in metabolites present in the urea and tricarboxylic acid (TCA) cycles. Peroxynitrite plasmatic levels were evaluated by a colorimetric method, final activity of superoxide dismutase (SOD) was evaluated by an enzymatic method, and mouse behavior was evaluated. Majority of the assay showed differences between control and treatment groups, as well as between genders. This may indicate the involvement of sex hormones in the regulation of a normal metabolic profile, and the implication of sex differences in metabolite disease response.

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