Barley consumption under a high-fat diet suppresses lipogenic genes through altered intestinal bile acid composition.

We evaluated whether barley flour consumption in a high-fat environment affects lipid metabolism through signals mediated by bile acids. Four-week-old mice were fed a high-fat diet supplemented with cellulose (HC) or ß-glucan-rich barley flour (HB) for 12 weeks. Bile acid composition in the intestinal tract and feces was measured by GC/MS. Gene expression levels involved in bile acid metabolism in the liver and intestinal tract were determined by RT-PCR. Similar parameters were measured in mice treated with antibiotics (antibiotics-cellulose [AC] and antibiotics-barley [AB]) to reduce the activity of intestinal bacteria. The Results showed that the HB group had lower liver blood cholesterol and triglyceride levels than the HC group. The HB group showed a significant decrease in primary bile acids in the gastrointestinal tract compared to the HC group. On the other hand, the concentration of secondary bile acids relatively increased in the cecum and feces. In the liver, Fxr activation suppressed gene expression levels in synthesizing bile acids and lipids. Furthermore, in the gastrointestinal tract, Tgr5 was activated by increased secondary bile acids. Correspondingly, AMP levels were increased in the HB group compared to the HC group, AMPK was phosphorylated in the liver, and gene expression involved in lipid synthesis was downregulated. A comparison of the AC and AB groups treated with antibiotics did not confirm these effects of barley intake. In summary, our results suggest that the prevention of lipid accumulation by barley consumption involves signaling through changes in bile acid composition in the intestinal tract.

A single administration of barley ß-glucan and arabinoxylan extracts reduces blood glucose levels at the second meal via intestinal fermentation.

Diet with barley may suppress the glycemic response after consuming the next meal ("second meal effect"). This study aimed to investigate the second meal effect and its mechanism. Mice were given a single dose of ß-glucan or arabinoxylan, the primary sources of soluble fiber in barley. A single dose of ß-glucan or arabinoxylan extract, followed 6 h later by a 20% glucose solution (second meal), suppressed blood glucose elevation. Arabinoxylan and ß-glucan increased the levels of short-chain fatty acids (SCFAs) in the ileum and cecum, respectively. Total GLP-1 secretion in the blood increased with ß-glucan and showed an increasing trend with arabinoxylan. These results suggest barley ß-glucan and arabinoxylan are fermented in the intestinal tract to generate SCFAs, which may induce GLP-1 secretion and control blood glucose levels during the second meal.

Consumption of barley flour increases gut fermentation and improves glucose intolerance via the short-chain fatty acid receptor GPR43 in obese male mice.

Barley consumption is expected to increase insulin sensitivity by increasing the level of short-chain fatty acids (SCFAs) and promoting the secretion of GLP-1. However, the involvement of GPR43, a receptor for SCFAs, has not been investigated. Therefore, we evaluated whether the inhibitory effect of ß-glucan-rich barley intake on blood glucose rise is mediated by GPR43 signalling via an increase of SCFAs. C57BL/6J mice and GPR43-knockout mice were fed high-fat diets with either cellulose (HC) or ß-glucan-rich barley flour (HB) for 12 weeks. The level of SCFAs in cecum contents was measured and the concentration of GLP-1 in the portal vein was determined. The supernatant of the cecum contents of C57BL/6J mice was added to GLUTag cells, and then the changes to GLP-1 and intracellular Ca2+ concentrations determined. The same parameters were measured using cells in which GPR43 was knocked down by siRNA. C57BL/6J mice fed HB diets showed a suppressed glucose rise compared to those on the HC diet. Cecum SCFAs and GLP-1 concentration in the portal vein were also increased by the HB diet. When an aqueous solution from the cecum content of mice fed a HB diet was added to GLUTag cells, GLP-1 secretion and intracellular Ca2+ concentration were increased. These phenomena were not observed in cells with knockdown of GPR43. In GPR43 knockout mice an increase of GLP-1 in the portal vein and suppression of blood glucose elevation was attenuated, despite increased SCFAs brought on by the HB diet. In conclusion, GPR43 activation in the intestinal tract via increased SCFAs is required for the glucose intolerance-improving effect of barley consumption.

Arabinoxylan as well as ß-glucan in barley promotes GLP-1 secretion by increasing short-chain fatty acids production.

Barley is rich in soluble dietary fiber including ß-glucan and arabinoxylan. Barley ß-glucan is fermented by gut bacteria and, thereby contributes to an effect on intestinal bacterial composition and short-chain fatty acids (SCFAs). It also increases GLP-1 secretion via SCFAs receptor. However, few studies have focused on barley arabinoxylan. Therefore, we have investigated the effects of arabinoxylan from barley on intestinal fermentability and GLP-1 secretion. C57BL/6J mice were fed a high-fat diet containing arabinoxylan-dominant barley flour without ß-glucan (bgl) and high ß-glucan-containing barley flour (BF) for 12 weeks. We conducted oral glucose tolerance test (OGTT) to measure insulin and GLP-1 concentrations. The concentration of SCFAs in the cecum contents was also determined. Furthermore, we measured mRNA expression assay GLP-1 secretion using real-time PCR. The OGTT result showed that GLP-1 concentrations at 60 min were increased in mice fed bgl and BF. Acetic acid and total SCFAs concentrations in the cecum contents were increased in both the barley groups, and butyric acid was increased in the bgl group. Furthermore, the bgl and BF groups had increased Gpr43, a receptor for SCFAs, and NeuroD which is involved in L cell differentiation. These results show arabinoxylan as well as ß-glucan is involved in the SCFAs-mediated increase in GLP-1 secretion upon barley consumption.

Microarray Analysis of Paramylon, Isolated from Euglena Gracilis EOD-1, and Its Effects on Lipid Metabolism in the Ileum and Liver in Diet-Induced Obese Mice.

We previously showed that supplementation of a high fat diet with paramylon (PM) reduces the postprandial glucose rise, serum total and LDL cholesterol levels, and abdominal fat accumulation in mice. The purpose of this study was to explore the underlying mechanism of PM using microarray analysis. Male mice (C57BL/BL strain) were fed an experimental diet (50% fat energy) containing 5% PM isolated from Euglena gracilis EOD-1 for 12 weeks. After confirming that PM had an improving effect on lipid metabolism, we assessed ileal and hepatic mRNA expression using DNA microarray and subsequent analysis by gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results suggested that dietary supplementation with PM resulted in decreased abdominal fat accumulation and serum LDL cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway. Postprandial glucose rise was reduced in mice fed PM, whereas changes in the glucose metabolism pathway were not detected in GO classification and KEGG pathway analysis. PM intake might enhance serum secretory immunoglobulin A concentrations via promotion of the immunoglobulin production pathway in the ileum.

Ingestion of High ß-Glucan Barley Flour Enhances the Intestinal Immune System of Diet-Induced Obese Mice by Prebiotic Effects.

The prebiotic effect of high ß-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.

Effects of ß-glucan Rich Barley Flour on Glucose and Lipid Metabolism in the Ileum, Liver, and Adipose Tissues of High-Fat Diet Induced-Obesity Model Male Mice Analyzed by DNA Microarray.

We evaluated whether intake of ß-glucan-rich barley flour affects expression levels of genes related to glucose and lipid metabolism in the ileum, liver, and adipose tissues of mice fed a high-fat diet. C57BL/6J male mice were fed a high-fat diet supplemented with high ß-glucan barley, for 92 days. We measured the expression levels of genes involved in glucose and lipid metabolism in the ileum, liver, and adipose tissues using DNA microarray and q-PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. The metabolic syndrome indices were improved by barley flour intake. Microarray analysis showed that the expression of genes related to steroid synthesis was consistently decreased in the liver and adipose tissues. The expression of genes involved in glucose metabolism did not change in these organs. In liver, a negative correlation was showed between some SCFAs and the expression levels of mRNA related to lipid synthesis and degradation. Barley flour affects lipid metabolism at the gene expression levels in both liver and adipose tissues. We suggest that SCFAs are associated with changes in the expression levels of genes related to lipid metabolism in the liver and adipose tissues, which affect lipid accumulation.

Low Molecular Weight Barley ß-Glucan Affects Glucose and Lipid Metabolism by Prebiotic Effects.

We investigated the effect of low molecular weight barley ß-glucan (LMW-BG) on cecal fermentation, glucose, and lipid metabolism through comparisons to high molecular weight ß-glucan (HMW-BG). C57BL/6J male mice were fed a moderate-fat diet for 61 days. LMW-BG or HMW-BG was added to the diet corresponding to 4% ß-glucan. We measured the apparent absorption of fat, serum biomarkers, the expression levels of genes involved in glucose and lipid metabolism in the liver and ileum, and bacterial counts of the major microbiota groups using real time PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. Significant reductions in serum leptin, total- and LDL-cholesterol concentrations, and mRNA expression levels of sterol regulatory element-binding protein-1c (SREBP-1c) were observed in both BG groups. HMW-BG specific effects were observed in inhibiting fat absorption and reducing abdominal deposit fat, whereas LMW-BG specific effects were observed in increasing bacterial counts of Bifidobacterium and Bacteroides and cecal total SCFAs, acetate, and propionate. mRNA expression of neurogenin 3 was increased in the LMW-BG group. We report that LMW-BG affects glucose and lipid metabolism via a prebiotic effect, whereas the high viscosity of HMW-BG in the digestive tract is responsible for its specific effects.