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.

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.

Effects of Daily Kelp (Laminaria japonica) Intake on Body Composition, Serum Lipid Levels, and Thyroid Hormone Levels in Healthy Japanese Adults: A Randomized, Double-Blind Study.

To investigate whether supplementation with iodine-reduced kelp (Laminaria japonica) powder decreases body fat composition in overweight Japanese subjects, a randomized, double-blind, placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥25 and <30 kg/m2. Subjects were randomly assigned to consume thirty tablets/d (10 tablets orally, 3 times/d) containing either iodine-reduced kelp powder (test, 6 g kelp powder corresponding to 3 g alginate/d) or kelp-free powder (placebo) for 8 weeks. Anthropometric measurements, blood lipids, and serum thyroid hormone levels were obtained before and after the trial. Body fat percentage was significantly decreased in male subjects from the test group compared with the placebo group. The same tendency was observed for body weight (p = 0.065) and BMI (p = 0.072) in male subjects. No significant changes in anthropometric measurements or visceral fat area were observed in female subjects. Serum thyroid hormone concentrations did not increase after 1.03 mg/d of iodine supplementation through kelp intake. The intake of iodine-reduced kelp powder led to significant and safe reductions in body fat percentage in overweight male subjects. The consumption of kelp high in alginate may contribute to preventing obesity without influencing thyroid function in Japanese subjects with a relatively high intake of iodine from seaweed.

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.

Effects of Paramylon Extracted from Euglena gracilis EOD-1 on Parameters Related to Metabolic Syndrome in Diet-Induced Obese Mice.

Paramylon (PM), a type of ß-glucan, functions like dietary fiber, which has been suggested to exert a protective effect against obesity. We evaluated the potential beneficial effects of PM powder on obesity in mice. Male C57BL/6J mice were fed a high-fat diet supplemented with either 2.5 or 5% PM powder, extracted from Euglena gracilis, for 74 days. Growth parameters, abdominal fat content, serum biochemical markers, hepatic lipid accumulation and hepatic mRNA expression were measured. Dietary supplementation with PM resulted in decreased food efficiency ratios and abdominal fat accumulation. Dose-dependent decreases were observed in postprandial glucose levels, serum low-density lipoprotein (LDL)-cholesterol, and serum secretary immunoglobulin A (sIgA) concentrations. PM supplementation increased peroxisome proliferator-activated receptor α (PPARα) mRNA expression in the liver which is suggested to induce ß-oxidation through activation of acyl-coenzyme A oxidase (ACOX), carnitine palmitoyltransferase (CPT) and fatty acid transport protein 2 (FATP2) mRNA expression. Changes in fatty acid metabolism may improve lipid and glucose metabolism. In conclusion, a preventive effect against obesity was observed in mice given a PM-enriched diet. The mechanism is suggested to involve a reduction in both serum LDL-cholesterol levels and the accumulation of abdominal fat, in addition to an improvement in postprandial glucose concentration.

Effects of BARLEYmax and high-ß-glucan barley line on short-chain fatty acids production and microbiota from the cecum to the distal colon in rats.

We investigated whether supplementation with the barley line BARLEYmax (Tantangara; BM), which contains three fermentable fibers (fructan, ß-glucan, and resistant starch), modifies the microbiota in cecal and distal colonic digesta in addition to short-chain fatty acids (SCFAs) production more favorably than supplementation with a high-ß-glucan barley line (BG012; BG). Male Sprague-Dawley rats were randomly divided into 3 groups that were fed an AIN-93G-based diet that contained 5% fiber provided by cellulose (control), BM or BG. Four weeks after starting the respective diets, the animals were sacrificed and digesta from the cecum, proximal colon and distal colon were collected and the SCFA concentrations were quantified. Microbiota in the cecal and distal colonic digesta were analyzed by 16S rRNA sequencing. The concentrations of acetate and n-butyrate in cecal digesta were significantly higher in the BM and BG groups than in the control group, whereas the concentration of total SCFAs in cecal digesta was significantly higher only in the BM group than in the control group. The concentrations of acetate and total SCFAs in the distal colonic digesta were significantly higher only in the BM group than in the control group. The abundance of Bacteroidetes in cecal digesta was significantly higher in the BM group than in the control group. In contrast, the abundance of Firmicutes in cecal digesta was significantly lower in the BM and BG groups than in the control group. These results indicated that BM increased the concentration of total SCFAs in the distal colonic digesta. These changes might have been caused by fructan and resistant starch in addition to ß-glucan. In conclusion, fermentable fibers in BM reached the distal colon and modified the microbiota, leading to an increase in the concentration of total SCFAs in the distal colonic digesta, more effectively compared with the high-ß-glucan barley line (BG).