Substitution of linoleic acid with α-linolenic acid or long chain n-3 polyunsaturated fatty acid prevents Western diet induced nonalcoholic steatohepatitis

Abstract

Imbalance in the n-6 polyunsaturated fatty acids (PUFA) and n-3 PUFA in the Western diet may increase the risk of nonalcoholic fatty liver disease (NAFLD). This study investigates the impact of substitution of linoleic acid with α-linolenic acid (ALA) or long chain (LC) n-3 PUFA and hence decreasing n-6:n-3 fatty acid ratio on high fat, high fructose (HFHF) diet induced nonalcoholic steatohepatitis (NASH). Male Sprague-Dawley rats were divided into four groups and fed control diet, HFHF diet (n-6:n-3 ratio of 200), HFHF diet with ALA (n-6:n-3 ratio of 2) or HFHF diet with LC n-3 PUFA (n-6:n-3 ratio of 5) for 24 weeks. Rats fed HFHF diet with n-6:n-3 ratio of 200 resulted in hepatic steatosis, induced glucose intolerance, insulin resistance and oxidative stress accompanied by increase in markers of inflammation, plasma lipids and aminotransferase levels. Histopathological examination of liver further confirmed the establishment of NASH. ALA and LC n-3 PUFA supplementation prevented hepatic steatosis and dyslipidemia by inhibiting lipogenesis and increasing insulin sensitivity. Furthermore, n-3 PUFA supplementation attenuated hepatic oxidative stress by restoring antioxidant status, decreased inflammation and preserved hepatic architecture. These finding suggest that decreasing n-6:n-3 ratio prevented HFHF induced NASH by attenuating oxidative stress and inflammation.

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

“…The quality of the consumed fatty acids (FAs) directly influences the adipose tissue, contributing to systemic inflammation through the secretion of pro-inflammatory adipocytokines, such as interleukin (IL)-6 and tumor necrosis factor α (TNF-α), and anti-inflammatory adipocytokines, such as IL-10 [1,5,6]. The state of low-grade inflammation is the pathological characteristic associated with chronical diseases such as obesity, metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), diabetes mellitus type 2 (DM2), and cardiovascular disease (CVD) [7][8][9].…”

“…Besides containing high concentrations of ALA, linseed oil contains high percentages of bioactive compounds that exert hypolipidemic and antioxidant actions. Its consumption is associated with the reduction in oxidative stress, arteriosclerosis, hypercholesterolemia, and hepatic steatosis [2,7,17,21]. In contrast, sesame oil, besides high quantities of PUFAs, contains lignans of sesamin, sesamolin, and homologues to tocopherol, which are related to improvement in the lipidic profile, reduction of blood glucose, and anti-inflammatory and antiproliferative properties in carcinogenic cells [22][23][24].…”

Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease

“…Moreover, a lipid signature that positions C14:0, C16:0, C16:1n-7, C18:1n-7, C18:1n-9 and C18:2n-6 as the main lipids that exhibit an accumulation during the NAFLD/NASH transition has also been characterized in NASH patients [280]. The fatty acids C16 and C18 are involved in the modulation of mitochondrial function [281], and their abnormal accumulation preceded oxidative stress and lipotoxicity [263,264,282]. Furthermore, a high-fat and high-cholesterol diet potentially contributes to hepatic steatosis and oxidative stress [174,265,283].…”

Omega-3 and omega-6 consumption in a sample group of portuguese women

“…These two fatty acids are indispensable for a set of organic functions, including: cell membrane formation, development of brain activity, elasticity and stiffness of blood vessels, gene expression and inflammatory response (4). The cell membrane PUFA composition is determined by the dietary levels of n-6 and n-3 PUFAs and their respective ratio (5). It is estimated that currently the common Western diet contributes to a relationship between n-3 and n-6 of 20-30:1, thus pointing to a 20 to 30-fold higher consumption of omegas 6 relative to n-3 consumption.…”

“…Estes dois ácidos gordos são indispensáveis para um conjunto de funções orgânicas, tais como: formação da membrana celular, desenvolvimento da atividade cerebral, elasticidade e rigidez dos vasos sanguíneos, expressão dos genes e a resposta inflamatória (4). A composição de AGPI da membrana celular é determinada pelos níveis dietéticos de AGPI n-6 e n-3 e a sua respetiva proporção (5). Estima-se que atualmente a dieta ocidental comum, contribua para uma relação entre os n-3 e n-6 de 20-30:1, apontando assim para um consumo 20 a 30 vezes superior de ómegas 6 relativamente ao consumo de n-3.…”