Anti-obesity Action of Fermented Barley Extracts with Lactobacillus plantarum dy-1 and Associated MicroRNA Expression in High-fat Diet-induced Obese Rats.

OBJECTIVE To further explore associated effects of Lactobacillus plantarum dy-1 (LFBE) on obesity and lipid metabolism at the gene expression level, the expression of microRNAs (miRNAs) was investigated in the liver of high-fat diet (HFD) induced obese rats. METHODS Three groups of animal models were established. Changes in miRNA expression in the liver of each group were analyzed by microarray and RT-qPCR, complemented by bioinformatics. Palmitateinduced hepatocellular carcinoma (HepG2) cells were used as a model to validate the test. RESULTS LFBE treatment groups and HFD groups were observed to be distinctly different with respect to rates of increase in body weight and body fat percentage and triglyceride (TG) and total cholesterol (TC) levels in serum and liver. In addition, the LFBE group showed upregulation of ten miRNAs and downregulation of five miRNAs in the liver. Downregulation of miR-34a and miR-212 was observed in the livers of the LFBE group. Gene ontology and kyoto encyelopedia of geues and genomes (KEGG) pathway analysis showed that possible target genes of the deregulated miRNAs were significantly enriched in the adrenergic and HIF-1 signaling pathways. CONCLUSION These results demonstrate that LFBE might regulate the expression of miRNAs in order to inhibit obesity and fatty liver.

[1]  Xiang Xiao,et al.  The anti-obesity effect of fermented barley extracts with Lactobacillus plantarum dy-1 and Saccharomyces cerevisiae in diet-induced obese rats. , 2017, Food & function.

[2]  Xiang Xiao,et al.  Dietary supplementation with Lactobacillus plantarum dy-1 fermented barley suppresses body weight gain in high-fat diet-induced obese rats. , 2016, Journal of the science of food and agriculture.

[3]  E. Monteiro,et al.  Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia , 2016, Respiratory Physiology & Neurobiology.

[4]  Yun Shi,et al.  β2-Adrenergic receptor ablation modulates hepatic lipid accumulation and glucose tolerance in aging mice , 2016, Experimental Gerontology.

[5]  H. Xin,et al.  Effect of miR-467b on atherosclerosis of rats. , 2016, Asian Pacific Journal of Tropical Medicine.

[6]  Wei Qiao,et al.  Anti-obesity and anti-diabetic effects of flavonoid derivative (Fla-CN) via microRNA in high fat diet induced obesity mice. , 2016, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[7]  Junjie Xiao,et al.  miR‐212 downregulation contributes to the protective effect of exercise against non‐alcoholic fatty liver via targeting FGF‐21 , 2015, Journal of cellular and molecular medicine.

[8]  K. Chowdhury,et al.  Vascular importance of the miR-212/132 cluster. , 2014, European heart journal.

[9]  Jin Chen,et al.  MicroRNA-212 Inhibits Osteosarcoma Cells Proliferation and Invasion by Down-Regulation of Sox4 , 2014, Cellular Physiology and Biochemistry.

[10]  Z. Madar,et al.  Mechanism for HIF-1 activation by cholesterol under normoxia: a redox signaling pathway for liver damage. , 2014, Free radical biology & medicine.

[11]  Yanlu Wang,et al.  MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation. , 2013, Biochemical and biophysical research communications.

[12]  B. Tzang,et al.  Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters. , 2013, Food chemistry.

[13]  M. Prentki,et al.  Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes , 2013, Diabetologia.

[14]  J. Hodgson,et al.  Supplementation of a high-fat diet with chlorogenic acid is associated with insulin resistance and hepatic lipid accumulation in mice. , 2013, Journal of agricultural and food chemistry.

[15]  I. Borecki,et al.  Genetic variants at PSMD3 interact with dietary fat and carbohydrate to modulate insulin resistance. , 2013, The Journal of nutrition.

[16]  Lin Zhao,et al.  Obesity and incidence of lung cancer: A meta‐analysis , 2013, International journal of cancer.

[17]  E. Gallagher,et al.  The increasing use of barley and barley by-products in the production of healthier baked goods , 2013 .

[18]  Dong-Hyun Kim,et al.  Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-Klotho , 2012, Proceedings of the National Academy of Sciences.

[19]  B. Tzang,et al.  Hypolipidemic and Antioxidative Effects of Noni (Morinda citrifolia L.) Juice on High- fat/Cholesterol-Dietary Hamsters , 2012, Plant Foods for Human Nutrition.

[20]  L. Eliasson,et al.  Differential Glucose-Regulation of MicroRNAs in Pancreatic Islets of Non-Obese Type 2 Diabetes Model Goto-Kakizaki Rat , 2011, PloS one.

[21]  Xian-gui Hu,et al.  MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer. , 2011, Biochemical and biophysical research communications.

[22]  A. Iyer,et al.  Fermented Wheat Germ Extract (Avemar) in the Treatment of Cardiac Remodeling and Metabolic Symptoms in Rats , 2011, Evidence-based complementary and alternative medicine : eCAM.

[23]  N. Ames,et al.  β-glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized, controlled trials , 2010, European Journal of Clinical Nutrition.

[24]  J. Yun Possible anti-obesity therapeutics from nature--a review. , 2010, Phytochemistry.

[25]  M. Jung,et al.  Consumption of barley beta-glucan ameliorates fatty liver and insulin resistance in mice fed a high-fat diet. , 2010, Molecular nutrition & food research.

[26]  B. Yandell,et al.  Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice , 2009, Mammalian Genome.

[27]  V. Fogliano,et al.  Cereal dietary fibre: a natural functional ingredient to deliver phenolic compounds into the gut , 2008 .

[28]  Richard J Jackson,et al.  How Do MicroRNAs Regulate Gene Expression? , 2007, Science's STKE.

[29]  Mark Graham,et al.  miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. , 2006, Cell metabolism.

[30]  R. Nicolosi,et al.  Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters. , 2004, The Journal of nutrition.

[31]  Yan Zhu,et al.  GW26-e4401 MiR-195-3p/-5p decrease cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts , 2015 .

[32]  Jaehwan Lee,et al.  Aqueous extracts of hulled barley containing coumaric acid and ferulic acid inhibit adipogenesis in vitro and obesity in vivo , 2015 .

[33]  S. Schinner Alterations in MicroRNA Expression Contribute to Fatty Acid–Induced Pancreatic β-Cell Dysfunction , 2009 .