Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and inflammation in mice

Abstract

Dietary intake of linoleic acid (LA) has increased dramatically during the twentieth century and is associated with a greater prevalence of obesity. Vegetable oils are recognised as suitable alternatives to fish oil (FO) in feed for Atlantic salmon (Salmo salar L.) but introduce high amounts of LA in the salmon fillet. The effect on fish consumers of such a replacement remains to be elucidated. Here, we investigate the effect of excessive dietary LA from soyabean oil (SO) on endocannabinoid levels in Atlantic salmon and mice, and study the metabolic effects in mice when SO replaces FO in feed for Atlantic salmon. Atlantic salmon were fed FO and SO for 6 months, and the salmon fillet was used to produce feed for mice. Male C57BL/6J mice were fed diets of 35% of energy as fat based on FO- and SO-enriched salmon for 16 weeks. We found that replacing FO with SO in feed for Atlantic salmon increased LA, arachidonic acid (AA), decreased EPA and DHA, elevated the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and increased TAG accumulation in the salmon liver. In mice, the SO salmon diet increased LA and AA and decreased EPA and DHA in the liver and erythrocyte phospholipids, and elevated 2-AG and AEA associated with increased feed efficiency, weight gain and adipose tissue inflammation compared with mice fed the FO salmon diet. In conclusion, excessive dietary LA elevates endocannabinoids in the liver of salmon and mice, and increases weight gain and counteracts the anti-inflammatory properties of EPA and DHA in mice.

Fig. 1

Levels of the n-6 fatty acids (a) linoleic acid (LA) and (b) arachidonic acid (AA), and the endocannabinoids (c) 2-arachidonoylglycerol (AG) and (d) anandamide (AEA) in the liver of Atlantic salmon fed soyabean oil (SO, ) and fish oil (FO, ). Values are means, with their standard errors represented by vertical bars. *Mean values were significantly different from those of SO-fed salmon (P<0.05).

Fig. 2

Changes in (a) linoleic acid (LA), (b) arachidonic acid (AA) in liver phospholipids (PL), (c) liver 2-arachidonoylglycerol (AG), cerebral (d) 2-AG and (e) anandamide (AEA), and (f) energy intake, (g) feed efficiency, (h) weight gain, (i) final body weight and (j) weekly body weight in mice fed the fish oil (FO, ) and soyabean oil (SO, ) salmon diets. Values are means, with their standard errors represented by vertical bars (n 8–9). *Mean values were significantly different from those of SO salmon-fed mice (P<0 05). BW, body weight.

Fig. 3

Histology of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) in mice fed the fish oil (FO) and soyabean oil (SO) salmon diets. (a) Immunostaining with the macrophage marker F4/80 in eWAT and iWAT of FO- and SO-fed mice. (b) Haematoxylin eosin (HE) staining and adipocyte size in eWAT and iWAT of mice fed the FO and SO salmon diets. Values are means, minimum and maximum ranges represented by vertical bars.