Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids

内科学 内分泌学 二十碳五烯酸 鱼油 多不饱和脂肪酸 内大麻素系统 脂肪组织 阿那达胺 欧米茄3脂肪酸 六烯酸 白色脂肪组织 生物 脂肪酸 化学 大麻素受体 医学 生物化学 受体 渔业 兴奋剂
作者
Helena L. Fisk,Caroline E. Childs,Elizabeth A. Miles,R. C. S. Ayres,Paul S. Noakes,Carolina Paras-Chavez,Ondřej Kuda,Jan Kopecký,Elie Antoun,Karen A. Lillycrop,Philip C. Calder
出处
期刊:Clinical Science [Portland Press]
卷期号:135 (1): 185-200 被引量:16
标识
DOI:10.1042/cs20201060
摘要

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/m2) and individuals living with metabolically healthy obesity (BMI 30–40 kg/m2) 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.
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