Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids. Issue 1 (15th January 2021)

• Record Type: Journal Article
• Authors: Fisk, Helena L.; Childs, Caroline E.; Miles, Elizabeth A.; Ayres, Robert; Noakes, Paul S.; Paras-Chavez, Carolina; Kuda, Ondrej; Kopecký, Jan; Antoun, Elie; Lillycrop, Karen A.; Calder, Philip C.
• Is Part Of: Clinical science. Volume 135:Issue 1(2021)
• Page Start: 185
• Page End: 200
• Publication Date: 2021-01-15
• Subjects: adipose tissue -- endocannabinoids -- LC n-3 PUFA -- lipids -- obesity; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20201060
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5–25 kg/m 2 ) and individuals living with metabolically healthy obesity (BMI 30–40 kg/m 2 ) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID ( PLA2G2D ) and phospholipase A2 Group IVA ( PLA2G4A ), and lower expression of CNR1 . In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.