Highland Barley Whole Grain ( Hordeum vulgare L.) Ameliorates Hyperlipidemia by Modulating Cecal Microbiota, miRNAs and AMPK Pathways in Leptin Receptor-Deficient db/db Mice

The mechanisms of highland barley whole grain (BWG) with rich phenolics on obese db/db mice were investigated in this study. Oral consumption of BWG reduced food intake, body weight, organ/body weight indexes of liver and fat, levels of serum and hepatic lipids, liver injury, and oxidative stress. Furthermore, BWG recovered the disorder of cecal microbiota by augmenting Bacteroidetes/Firmicutes ratio and Alistipes abundance, and decreasing abundances of Bacteroides and Desulfovibrionaceae to regulate lipid metabolism-related genes. BWG inhibited fatty acid biosynthesis via up-regulating the phosphorylation of AMP-activated protein kinase α (AMPKα), while down-regulating sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1) levels. BWG also significantly down-regulated miRNA-122, miRNA-33, miRNA-34a and miRNA-206 levels. Accordingly, BWG exhibited hypolipidemic potential through modulating cecal microbiota, AMPK/SREBP-1c/FAS pathway and related miRNAs, triggering the alleviation of dyslipidemia. These findings suggested BWG as an effective candidate to ameliorate the symptoms of hyperlipidemia.