Dietary Flaxseed Oil Prevents Western‐Type Diet‐Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein‐E Knockout Mice

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD).

Dietary fat composition: replacement of saturated fatty acids with PUFA as a public health strategy, with an emphasis on α-linolenic acid

“…In addition, recent evidence suggests an alternate mechanism of action whereby ALA attenuates the NLRP3 inflammasome through activation of the PPARγ pathway (87) . Similar beneficial effects on HFD-induced hepatic steatosis, inflammation and lipid homoeostasis were observed following substituting of 10 % of HFD with ALA for 12 weeks (91)(92)(93)(94) . Furthermore, ALA has been associated with improvements in CVD risk factors.…”

Chia (Salvia hispanica)-supplemented diet ameliorates non-alcoholic fatty liver disease and its metabolic abnormalities in humans

“…Evaluation of a dietary pattern study showed that patients with NAFLD had a high consumption of omega-6 polyunsaturated fatty acids [27]. Moreover, in animal models, reduction in the omega-6: omega-3 index decreases the intra-hepatic fat content [4,28], independently of the bio-conversion of ALA to EPA and DHA [29]. These findings support the current observations regarding a significant reduction in the omega-6: omega-3 index, accompanied by an amelioration in the liver:spleen attenuation ratio.…”

Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet

“…These results are in accordance with the previous study’s findings [39] that upregulation of PPAR evokes β-oxidation of fatty acids, increasing glucose uptake and catabolism, and in turn alleviates NALFD and improves IR. To our knowledge, most studies showed improved insulin sensitivity and lipid metabolism via PPAR-α target genes, CPT-1, and MCAD [40, 41], while few carried on with PPAR-γ / CPT-1/ MCAD signaling in the liver. This was partially done because PPAR-γ is mainly expressed in the adipose tissue, playing a vital role in the whole body lipid metabolism and insulin sensitivity [27].…”