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 A 2 Group IID ( PLA2G2D ) and phospholipase A 2 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.

Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 ( r = 0.580; P < 0.001) and sVCAM-1 ( r = 0.392; P < 0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin ( r = 0.234; P = 0.027) was lost when other variables were controlled for. Male subjects < 40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males > 55 years of age (both P < 0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance ( P = 0.073). Subgroups of 16 males aged < 40 years and 12 elderly subjects (> 55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males ( P = 0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects ( P = 0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects ( P = 0.043), with a median decrease of 20% (range 16–60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.