Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE−/− Mice

Abstract

Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic Apolipoprotein E (ApoE)−/− mice. In the initial portion, the ApoE−/− mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated ApoE−/− mice were divided into two groups: AB-treated model group (AB/MOD) and FO-fed AB-treated model group (AB/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic/vascular inflammatory cytokines and in situ macrophages (Mψs) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in ApoE−/− mice via the gut microbiota-inflammation-artery axis.

Dietary Ground Flaxseed Increases Serum Alpha-Linolenic Acid Concentrations in Adult Cats

“…However, the use of flaxseed as a source of omega-3 fatty acids, and in particular the fatty acid ALA, in cat diets is often dismissed due to their inability to convert ALA to EPA and DHA. More recent evidence in human, companion animal, and pre-clinical models suggests that ALA itself has immunomodulatory benefits [ 5 , 13 , 21 , 22 ]. Although it has been reported that cats have low delta-6 desaturase activity, there is evidence that at least in liver and brain tissue specifically, synthesis of long-chain omega-3 fatty acids can be achieved in the absence of dietary EPA, DPA, and DHA in cats [ 23 ].…”

Butyrate suppresses atherosclerotic inflammation by regulating macrophages and polarization via GPR43/HDAC-miRNAs axis in ApoE−/− mice

“…The fresh feces of each group were individually collected and immediately frozen into liquid nitrogen, finally stored at −80˚C until the DNA extraction. Cetyltrimethylammonium bromide (CTAB) method [29] was used to extract the genomic DNA of samples, and then the purity and concentration of the DNA were detected by agarose gel electrophoresis and Nanodrop one (Thermo Fisher, USA). Briefly, 16S rRNA genes were amplified by using V3-V4 regions bacterial primers (341F 5'-CCTAYGGGRBGCASCAG-3' and 806R 5'-GG ACTACNNGGGTATCTAAT-3').…”

The role of the gut microbiota in health and cardiovascular diseases

“…Many studies have fully investigated the role of probiotics in the prevention and treatment of atherosclerosis [ 532 – 534 ]. For example, Lactobacillus can regulate gut microbiota structure and its metabolites, and improve lipid metabolism and serum TMAO levels [ 535 ].…”