Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study.
Souza, PR, Marques, RM, Gomez, EA, Colas, RA, De Matteis, R, Zak, A, Patel, M, Collier, DJ, Dalli, J
Circulation research. 2020;126(1):75-90
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Specialized pro-resolving mediators (SPM) are derived from essential fatty acids and promote resolution of inflammation. The main aim of this study was to establish the relationship(s) between supplement dose, peripheral blood SPM concentrations, and cellular responses using a novel enriched marine oil preparation. This study is a double-blind, randomized, crossover, dose escalation placebo-controlled study in healthy volunteers. Participants (n=22) were randomised to one of eight groups. Results show supplementation with refined marine oils lead to a rapid upregulation of peripheral blood SPM concentrations and reprograming of peripheral blood cell responses to sterile and infectious stimuli, changes that were found to persist after SPM concentrations returned to baseline. Authors conclude that enriched marine oil supplementation leads to a dose-and time-dependent increase of plasma SPM concentrations.
RATIONALE Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. OBJECTIVE Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. METHODS AND RESULTS Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo. CONCLUSIONS Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.
Immunohistochemical identification of the beta(3)-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine.
De Matteis, R, Arch, JR, Petroni, ML, Ferrari, D, Cinti, S, Stock, MJ
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2002;(11):1442-50
OBJECTIVES To investigate whether the beta(3)-adrenoceptor could be identified by immunohistochemistry in intact human white and brown adipocytes and other human tissues, and to investigate the influence of obesity and its treatment with ephedrine and caffeine on the expression of the beta(3)-adrenoceptor in adipocytes. METHODS Morbidly obese patients were given a hypoenergetic diet (70% of energy expenditure) and some were also treated with ephedrine and caffeine (20/200 mg, three times daily) for 4 weeks. Adipose tissue and other tissues were taken during surgery. Immunohistochemistry was carried out using a monoclonal antibody raised against the human beta(3)-adrenoceptor. RESULTS Staining was localized to the periphery of cells. All white adipocytes were stained. Those from lean subjects and obese subjects treated with ephedrine and caffeine showed more intense staining than those from untreated obese subjects. Staining was more intense in brown than in white adipocytes in perirenal adipose tissue from phaeochromocytoma patients. Staining was also seen in ventricular myocardium, and in smooth muscle of the prostate, ileum, colon and gall bladder. DISCUSSION The tissue and subcellular distribution of staining was consistent with it being due to binding of the antibody to the human beta(3)-adrenoceptor. The presence of the beta(3)-adrenoceptor in human white adipocytes is consistent with evidence that it can mediate lipolysis in human white adipocytes. The increased expression of the beta(3)-adrenoceptor in obese subjects treated with caffeine and ephedrine supports the potential of beta(3)-adrenoceptor agonists in the treatment of obesity and type 2 diabetes. Its expression in ventricular myocardium is consistent with evidence that the beta(3)-adrenoceptor mediates a negative inotropic effect in this tissue.