Nutrients. , 2019., Dec 18;12(1). pii: E9. doi: 10.3390/nu12010009.

Protective Effect of α-Linolenic Acid on Non-Alcoholic Hepatic Steatosis and Interleukin-6 and -10 in Wistar Rats.

Jordão Candido C Silva Figueiredo P Del Ciampo Silva R et al.

Abstract

Consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) is related to improvement in the inflammatory response associated with decreases in metabolic disorders of obesity, such as low-grade inflammation and hepatic steatosis. Linseed (Linum usitatissimum) oil is a primary source of n-3 fatty acids (FAs) of plant origin, particularly α-linolenic acid, and provides an alternative for the ingestion of n-3 PUFA by persons allergic to, or wishing to avoid, animal sources. In our study, we evaluated the effect of the consumption of different lipidic sources on metabolic and inflammatory parameters in Wistar rats. We split 56 male rats into four groups that were fed for 60 days with the following diets: sesame oil, (SO, Sesamum indicum), linseed oil (LO), SO + LO (SLO), and a control group (CG) fed with animal fat. Our results reveal that the use of LO or SLO produced improvements in the hepatic tissue, such as lower values of aspartate aminotransferase, liver weight, and hepatic steatosis. LO and SLO reduced the weight of visceral fats, weight gain, and mediated the inflammation through a decrease in interleukin (IL)-6 and increase in IL-10. Though we did not detect any significant differences in the intestine histology and the purinergic system enzymes, the consumption of α-linolenic acid appears to contribute to the inflammatory and hepatic modulation of animals compared with a diet rich in saturated FAs and or unbalanced in n-6/n-3 PUFAs, inferring possible use in treatment of metabolic disorders associated with obesity and cardiovascular diseases.

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Key Points

The FAs of the n-3 series are capable of minimizing the acute and chronic inflammation through various associated effects, whereas the eicosanoids derived from the excess of n-6 PUFAs formed in the organism are potent mediators of thrombosis and inflammation. The mechanisms of the effects of n-3 can include a change in the composition of lipidic membranes, higher energetic expenditure, less formation of reactive oxygen species (ROS), and activation of peroxisome proliferator-activated receptor (PPAR), which act to decrease the activation of inflammatory pathways, such as c-Jun N terminal kinase (JNK) and nuclear factor-κB (NF-κB). Moreover, signaling modular molecules regulate the function of the immune system cells through liberation of cytokines, cell differentiation, and platelet aggregation.

the use of PUFAs of plant origin as a lipid source in Wistar rats evidenced by the positive effects on the lipid and glycemic profile. The objective of this study was to investigate the effect of linseed and sesame oils, sources of ALA and n-6 PUFA, respectively, on target organs and the inflammatory mediation of the metabolism of Wistar rats.

 

The decrease of SFA and increase of PUFA in the diet of animals promoted an improvement in the biochemical, inflammatory, and histopathological parameters. The effects were more pronounced when the proportion of n-3 PUFA series was higher than that of the n-6 PUFA series.  At the end of the 60 day experiment, the rats fed with the diets rich in PUFAs exhibited lower accumulated body weight, liver weight, and deposits of visceral fats, only showing alterations in the used lipid sources, without changes in the proportion or caloric value. Those rats presented the lowest weight gain, fat content in carcass, and serum levels of triglycerides (TG), AST, and total cholesterol.  The higher quantity of ALA in LO provided an omega-6:omega-3 ratio of approximately 1:3, whereas the ratio in SLO was close to 1:1, supporting the finding that the lower the proportion of omega-6 to omega-3, the stronger the hepatoprotective effect.  Lower values of weight gain, AST, IL-6, and hepatic steatosis were directly correlated with the increase in PUFAs in the diets, and especially n-3 PUFA ALA, which was the major lipid source in the LO diet. A diet with higher quantities of omega-3 promoted improvement in all evaluated biochemical, inflammatory, and histopathological parameters. The consumption of linseed oil, rich in n-3 PUFAs, primarily ALA, was found to be beneficial for decreases in body weight gain and visceral fats. The results demonstrate a direct connection with the lower expression of pro-inflammatory IL-6 and increase of anti-inflammatory IL-10, and lower values of AST with the reduction of hepatic steatosis.