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Endocannabinoid system and cardiometabolic risk factors: A comprehensive systematic review insight into the mechanistic effects of omega-3 fatty acids

Saleh-Ghadimi, Sevda, Kheirouri, Sorayya, Maleki, Vahid, Jafari-Vayghan, Hamed, Alizadeh, Mohammad
Life sciences 2020 v.250 pp. 117556
T-lymphocytes, adiposity, anti-inflammatory activity, cannabinoids, cytokines, databases, drugs, glucose, homeostasis, humans, inflammation, omega-3 fatty acids, oxylipins, randomized clinical trials, risk factors, systematic review, therapeutics, weight gain
Increased levels of endocannabinoids, 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA) have a pathophysiological role in the setting of cardiometabolic diseases. This systematic review was carried out to appraise the effect of omega-3 on cardiometabolic risk factors by highlighting the mediating effect of endocannabinoids. SCOPUS, PubMed, Embase, Google Scholar and ProQuest databases were searched until January 2020. All published English-language animal studies and clinical trials that evaluated the effects of omega-3 on cardiometabolic diseases with a focus on endocannabinoids were included. Of 1407 studies, 16 animal studies and three clinical trials were included for analysis. Eleven animal studies and two human studies showed a marked reduction in 2-AG and AEA levels following intake of omega-3 which correlated with decreased adiposity, weight gain and improved glucose homeostasis. Moreover, endocannabinoids were elevated in three studies that replaced omega-3 with omega-6. Omega-3 showed anti-inflammatory properties due to reduced levels of inflammatory cytokines, regulation of T-cells function and increased levels of eicosapentaenoyl ethanolamide, docosahexaenoyl ethanolamide and oxylipins; however, a limited number of studies examined a correlation between inflammatory cytokines and endocannabinoids following omega-3 administration. In conclusion, omega-3 modulates endocannabinoid tone, which subsequently attenuates inflammation and cardiometabolic risk factors. However, further randomized clinical trials are needed before any recommendations are made to target the ECS using omega-3 as an alternative therapy to drugs for cardiometabolic disease improvement.