Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids
Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids
复制标题
肥胖人群皮下脂肪组织内源性大麻素浓度失调及 omega-3 多不饱和脂肪酸的调节
DOI：
10.1042/cs20201060
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发表时间：
2021-01-01
期刊：
影响因子：
6
通讯作者：
Calder, Philip C.
中科院分区：
文献类型：
--
作者：
Fisk, Helena L.;Childs, Caroline E.;Calder, Philip C.
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，在人类白色脂肪组织（WAT）中的报告是有限的和不确定的。海洋长链ω-3多不饱和脂肪酸（LC n-3 PUFA）具有抗炎作用，因此可以改善肥胖相关的脂肪组织炎症。因此，脂肪酸（FA）浓度，内源性大麻素浓度，在来自健康正常体重个体的皮下WAT（scWAT）活组织检查中评估基因表达（BMI 18.5-25 kg/m2）和代谢健康型肥胖患者（BMI 30-40 kg/m（2））在12周的干预之前和之后，每天服用3 g鱼油（1.1 g二十碳五烯酸（EPA）+ 0.8 g DHA）或3 g玉米油（安慰剂）。来自代谢健康肥胖个体的WAT具有较高的n-6 PUFA和EPA，较高浓度的两种内源性大麻素（花生四烯酸（AEA）和二十碳五烯酰乙醇酰胺（EPEA）），较高表达的磷脂酶A2组IID（PLA 2G 2D）和磷脂酶A2组IVA（PLA 2G 4A），以及较低表达的CNR 1。在鱼油干预的反应中，WAT EPA在两个BMI组中增加到相似的程度，而WAT DHA在正常体重的个体中增加的程度更大。WAT EPEA和二十二碳六烯酰乙醇酰胺（DHEA）仅在正常体重个体中增加，而WAT 2-花生四烯酰甘油（2-AG）仅在代谢健康的肥胖个体中减少。基线代谢健康的肥胖患者中WAT脂肪酸、内源性大麻素和基因表达谱的改变可能与此相关。WAT结合n-3 PUFA，当它们的摄入量增加时，会影响内源性大麻素系统;然而，在正常体重的个体中的影响似乎比代谢健康的肥胖者更大。
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.