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

J Agric Food Chem. 2020 Oct 21;68(42):11735-11746. doi: 10.1021/acs.jafc.0c04780. Epub 2020 Oct 7.

Abstract

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 the Bacteroidetes/Firmicutes ratio and Alistipes abundance and decreasing the abundances of Bacteroides and Desulfovibrionaceae to modulate lipid metabolism-related genes. BWG inhibited fatty acid biosynthesis via upregulating the phosphorylation of AMP-activated protein kinase α, while downregulating sterol regulatory element binding protein-1c, fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 levels. BWG also significantly downregulated 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.

Keywords: AMPK pathway; cecal microbiota; highland barley; hyperlipidemia; miRNAs; whole grain.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Cecum / metabolism
  • Cecum / microbiology*
  • Disease Models, Animal
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Gastrointestinal Microbiome*
  • Hordeum / metabolism*
  • Humans
  • Hyperlipidemias / diet therapy*
  • Hyperlipidemias / genetics
  • Hyperlipidemias / metabolism
  • Hyperlipidemias / microbiology
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Receptors, Leptin / deficiency*
  • Receptors, Leptin / genetics
  • Seeds / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism

Substances

  • MicroRNAs
  • Receptors, Leptin
  • Sterol Regulatory Element Binding Protein 1
  • leptin receptor, mouse
  • Fatty Acid Synthases
  • AMP-Activated Protein Kinases