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肥胖症患者人体皮下脂肪组织中环腺苷酸浓度的失调及ω-3 多不饱和脂肪酸的调节作用。

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

机构信息

School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.

出版信息

Clin Sci (Lond). 2021 Jan 15;135(1):185-200. doi: 10.1042/CS20201060.

DOI:10.1042/CS20201060
PMID:33393630
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.

摘要

肥胖被认为与内源性大麻素系统失调有关,这可能反映了炎症的增强。然而,目前关于人类白色脂肪组织(WAT)中这种情况的报告有限且尚无定论。海洋长链 ω-3 多不饱和脂肪酸(LC n-3 PUFAs)具有抗炎作用,因此可能改善与肥胖相关的脂肪组织炎症。因此,在一项为期 12 周的干预研究中,评估了健康正常体重个体(BMI 18.5-25 kg/m2)和患有代谢健康肥胖个体(BMI 30-40 kg/m2)的皮下 WAT(scWAT)活检中的脂肪酸(FA)浓度、内源性大麻素浓度和基因表达,这些个体在干预前和干预后分别接受了 3 克鱼油/天(1.1 克二十碳五烯酸(EPA)+0.8 克二十二碳六烯酸(DHA))或 3 克玉米油/天(安慰剂)。患有代谢健康肥胖的个体的 WAT 中含有更高的 n-6 多不饱和脂肪酸和 EPA,更高浓度的两种内源性大麻素(花生四烯酸酰胺(AEA)和二十碳五烯酰乙醇胺(EPEA)),更高的磷脂酶 A2 组 IID(PLA2G2D)和磷脂酶 A2 组 IVA(PLA2G4A)表达,以及更低的 CNR1 表达。对鱼油干预的反应,WAT 中的 EPA 在两组 BMI 个体中增加到相似的程度,而 WAT 中的 DHA 在正常体重个体中增加的程度更大。只有在正常体重个体中,WAT 中的 EPEA 和二十二碳六烯酰乙醇胺(DHEA)增加,而只有在患有代谢健康肥胖的个体中,WAT 中的 2-花生四烯酰甘油(2-AG)减少。基线时代谢健康肥胖个体的 WAT 脂肪酸、内源性大麻素和基因表达谱的改变可能有关联。当摄入增加时,WAT 会摄入更多的 n-3 PUFA,这会影响内源性大麻素系统;然而,在正常体重个体中的影响似乎大于患有代谢健康肥胖的个体。

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