Beneficial effects of fermented barley extracts on inflammatory status and gut microbiota in high-fat diet-induced obese rats.

AIMS: To explore how fermented barley extracts could affect obesity-associated inflammatory responses to ameliorate high-fat diet (HFD)-induced obesity, and investigate whether their anti-inflammatory properties were affected by modulating the gut microbiota. METHODS AND RESULTS: Twenty-four male rats were assigned randomly to three groups for 8 weeks. Inflammatory status and gut microbiota in HFD-induced obese rats were measured by enzyme linked immunosorbent assay and 16sRNA sequencing technology. The dietary supplementation of Extract of fermented barley with L. plantarum JDM1 (LFBE) reduced HFD-induced obesity and improved insulin sensitivity. LFBE significantly decreased the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines (tumour necrosis factor-α, interleukin [IL]-6, IL-1ß, monocyte chemotactic protein-1), and increased anti-inflammatory cytokines (IL-10) in serum. In addition, LFBE suppressed the activation of nuclear factor-κB (NF-κB) by inhibiting the inhibitor of NF-κB alpha degradation and phosphorylation of JNK/p38 mitogen-activated protein kinases in adipose tissue. Combined with changes in gut microbiota, these results illustrated that LFBE treatment markedly decreased the proportion of the LPS-producing opportunistic pathogens and increased the proportion of Bifidobacterium. CONCLUSIONS: Administration of LFBE has beneficial effects on ameliorating HFD-induced obesity and insulin resistance, lessening HFD-induced gut microbiota dysbiosis and pro-inflammatory cytokines secretion. SIGNIFICANCE AND IMPACT OF THIS STUDY: The results suggest that fermented barley extracts may be a useful functional compound and beneficial to improve inflammatory status and gut microflora.

Effects of a pyroglutamyl pentapeptide isolated from fermented barley extract on atopic dermatitis-like skin lesions in hairless mouse.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic and eczematous skin lesions. The skin of AD patients is generally in a dried condition. Therefore, it is important for AD patients to manage skin moisturization. In this study, we examined the effects of orally administered fermented barley extract P (FBEP), which is prepared from a supernatant of barley shochu distillery by-product, on stratum corneum (SC) hydration and transepidermal water loss (TEWL) in AD-like lesions induced in hairless mice using 2,4,6-trinitrochlorobenzene. Oral administration of FBEP increased SC hydration and decreased TEWL in the dorsal skin of this mouse model. Further fractionation of FBEP showed that a pyroglutamyl pentapeptide, pEQPFP comprising all -L-form amino acids, is responsible for these activities. These results suggested that this pyroglutamyl pentapeptide may serve as a modality for the treatment of AD.

Laxative effects of triple fermented barley extracts (FBe) on loperamide (LP)-induced constipation in rats.

BACKGROUND: Constipation, a common health problem, causes discomfort and affects the quality of life. This study intended to evaluate the potential laxative effect of triple fermented barley (Hordeum vulgare L.) extract (FBe), produced by saccharification, Saccharomyces cerevisiae, and Weissella cibaria, on loperamide (LP)-induced constipation in Sprague-Dawley (SD) rats, a well-established animal model of spastic constipation. METHODS: Spastic constipation was induced via oral treatment with LP (3 mg/kg) for 6 days 1 h before the administration of each test compound. Similarly, FBe (100, 200 and 300 mg/kg) was orally administered to rats once a day for 6 days. The changes in number, weight, and water content of fecal, motility ratio, colonic mucosa histology, and fecal mucous contents were recorded. The laxative properties of FBe were compared with those of a cathartic stimulant, sodium picosulfate. A total of 48 (8 rats in 6 groups) healthy male rats were selected and following 10 days of acclimatization. Fecal pellets were collected one day before administration of the first dose and starting from immediately after the fourth administration for a duration of 24 h. Charcoal transfer was conducted after the sixth and final administration of the test compounds. RESULTS: In the present study, oral administration of 100-300 mg/kg of FBe exhibited promising laxative properties including intestinal charcoal transit ratio, thicknesses and mucous producing goblet cells of colonic mucosa with decreases of fecal pellet numbers and mean diameters remained in the lumen of colon, mediated by increases in gastrointestinal motility. CONCLUSION: Therefore, FBe might act as a promising laxative agent and functional food ingredient to cure spastic constipation, with less toxicity observed at a dose of 100 mg/kg.

Fermented Barley Extracts with Lactobacillus plantarum dy-1 Rich in Vanillic Acid Modulate Glucose Consumption in Human HepG2 Cells.

OBJECTIVE: To investigate the effect of fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) for modulating glucose consumption in HepG2 cells via miR-212 regulation. METHODS: Hepatocellular carcinoma (HepG2) cells were treated with palmitate. After 12 h, palmitate-induced HepG2 cells were treated with LFBE and its main components. Changes in glucose consumption, proinflammatory cytokine secretion, and miRNA-212 expression in HepG2 cells was observed. RESULTS: Treatment with LFBE rich in vanillic acid (VA) increased glucose consumption and reduced proinflammatory cytokine secretion in HepG2 cells. LFBE and VA normalized the upregulation of miR-212, which led to the upregulation of dual-specificity phosphatase-9 (DUSP9), a direct target of miR-212, at both protein and mRNA levels. Downregulation of miR-212 markedly increased glucose consumption and reduced proinflammatory cytokine secretion by enhancing DUSP9 expression. CONCLUSION: The results showed the benefit of LFBE and miR-212 downregulation in modulating glucose consumption and reducing proinflammatory cytokine secretion by targeting DUSP9. VA in LFBE was a strong regulator of palmitate-induced abnormal glucose consumption in HepG2 cells and can be a primary mediator.

Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Barley Extract in the Transplantation Tumor Model of Human HT-29 Cells in Nude Mice.

OBJECTIVE: A subcutaneous transplantation tumor model of human HT-29 cells was established in nude mice to study the anticarcinogenic activities and apoptosis-regulatory mechanistic effect of aqueous extract of fermented barley with Lactobacillus plantarum dy-1 (LFBE). METHODS: HT-29 cells were transplanted via subcutaneous injection of 1 × 107cells into the right flank of each nude mouse. Then, nude mice were treated for 30 days with LFBE (high-dose 2 g·kg-1·d-1; low-dose 1 g·kg-1·d-1) and for 7 days with 5-fluorouracil (5-FU, 25 g·kg-1·d-1) by gavage and intraperitoneal injection, respectively. RESULTS: Tumor volume and weight decreased significantly in both groups of nude mice treated with LFBE. In addition, the cell apoptosis rate of the LFBE group was significantly higher than that of the control group and 5-FU groups as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot methods further confirmed these apoptosis-enhancing and growth-inhibiting effects. The involvement of LFBE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, caspase-3, and cyclinD1. CONCLUSION: The results showed that LFBE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be used as a natural nutrient supplement or chemopreventive agent in the treatment of human colon cancer.

Dietary supplementation with Lactobacillus plantarum dy-1 fermented barley suppresses body weight gain in high-fat diet-induced obese rats.

BACKGROUND: Cereal fermentations have shown significant potential in improvement and design of the nutritional quality and health effects of foods and ingredients. In the present study, the effect of supplementary Lactobacillus plantarum dy-1 fermented barley (LFB) on obesity in high-fat diet (HFD)-induced obese rats was investigated. RESULTS: LFB treatment showed a lower rate of increase in body weight and percentage of body fat and a reversal of HFD-induced glucose intolerance, with ameliorated hyperinsulinemia, decreased levels of triglycerides and total cholesterol, and inhibited concentration of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α. Moreover, LFB treatment also showed the strongest inhibition of nuclear factor (NF)-kB activation and exhibited the greatest effects in blocking the degradation of the inhibitor of NF-kB and inhibiting p38 and JNK1 phosphorylation compared with HFD and raw barley treatment. CONCLUSIONS: It was clear that Lactobacillus plantarum dy-1 fermentation significantly improves the anti-obesity properties of barley. The results establish the foundation for ameliorating diet-induced obesity of product with LFB as nutritional supplements. © 2016 Society of Chemical Industry.

Fermented barley extract supplementation ameliorates metabolic state in stroke-prone spontaneously hypertensive rats.

We studied the effects of fermented barley extract P (FBEP) in stroke-prone spontaneously hypertensive rats (SHRSP). Male 10-week-old SHRSP were divided into three groups that were fed: an AIN-93M diet (control), a low dose of FBEP (4 g/kg; FBEP1), and a high dose of FBEP (20 g/kg; FBEP2) for three weeks. Hypertension was significantly improved by the use of FBEP supplementation. The FBEP diet improved plasma triglyceride, insulin sensitivity, enhanced plasma catalase, and superoxide dismutase activities, and decreased plasma 8-hydroxy-2'-deoxyguanosine levels. In addition, the FBEP diet upregulated hepatic antioxidative genes and modulated Nrf2 protein levels in the liver. Furthermore, a single oral dose of FBEP (2 g/kg body weight) was able to lower blood pressure in SHRSP. In conclusion, our data suggest that increased expression of hepatic antioxidative genes and modulation of Nrf2 may play a role in the regulation of metabolic diseases in SHRSP consuming a FBEP diet.

Study on the Mechanism of Effect of Protein on Starch Digestibility in Fermented Barley.

Previous studies have shown that fermented barley has a lower digestion rate. However, it remains unclear whether the antidigestibility of starch in fermented barley is affected by other nonstarch components. In this paper, the removal of protein, lipid, and ß-glucan improved the hydrolysis rate of starch and the protein showed the greatest effect. Subsequently, the inhibitory mechanism of protein on starch digestion was elucidated from the perspective of starch physicochemical properties and structural changes. The removal of protein increased the swelling power of starch from 10.09 to 11.14%. The short-range molecular ordered structure and the helical structure content decreased. The removal of protein reduced the coating and particle size of the starch particles, making the Maltese cross more dispersed. In summary, protein in fermented barley enhanced the ordered structure of starch by forming a physical barrier around starch and prevented the expansion of starch, which inhibited the hydrolysis of starch.

Purification and Identification of Lipid-Lowering Protein from Barley Extract after Lactiplantibacillus plantarum dy-1 fermentation.

Previous studies have found that the protein in barley extract fermented by Lactiplantibacillus plantarum dy-1 has the ability to inhibit lipid accumulation. However, the isolation, purification, and structural identification of the protein with lipid-lowering activity were still needed. In the present study, barley protein fermented by L. plantarum dy-1 with the optimal lipid-lowering ability was isolated and purified in three steps: using ammonium sulfate precipitation, anion-exchange chromatography, and size-exclusion chromatography. Combined with the model of HepG2 cells induced by oleic acid, the results showed that the pure protein LFBEP-C1 had the best lipid-lowering potential. Furthermore, our research found that LFBEP-C1 enriched the content of hydrophobic amino acids in LFBEP-C1. Ultraviolet spectroscopy analysis indicated that the glycosidic bond in LFBEP-C1 was an O-type glycosidic bond. The FTIR and circular dichroism spectra indicated that α-helix and random coil were the main secondary structures of LFBEP-C1. Mass spectrometry determined the theoretical molecular weight of LFBEP-C1 as 48 kDa, and its amino acid coverage was 63%. These findings suggest that the protein LFBEP-C1 with the best lipid-lowering activity was isolated and purified, and its structural characteristics were identified.

Supplementation with Fermented Barley Extract Prevents Mammary Epithelial Cell Invasion in an Early Breast Cancer Model.

Diet-based prevention of malignant transformation contributes to the maintenance of quality of life by avoiding a battle against cancer. Invasion is one of the features of malignant breast cancer, and the prevention of invasion may reduce breast cancer malignancy. A recently established early breast cancer model system showed mammary ductal dysplasia with invasion in mice. This study utilized the model system and investigated the effect of fermented barley extract (FBE), a food material. The elastic fiber layer is the outermost layer of the mammary duct. A reduction in the elastic fiber layer was observed in the mammary glands of the model system, whereas supplementation with 8% FBE containing water prevented this reduction. Moreover, we found that FBE supplementation prevented mammary epithelial cell invasion. Based on our findings, FBE might be a candidate material for a diet-based prevention of early breast cancer invasion.

The effect of sigumjang (Korean fermented barley bran) marination on the physicochemical properties of pork loin.

Sigumjang is a traditional Korean fermented barley bran consumed in the Gyungsang-do area. In this study, pork loin was marinated with sigumjang, and its physicochemical and textural properties were investigated. Sigumjang-marinated pork loin (SMPL) displayed an attractive yellowish-brown overall color. SMPL's pH marginally increased during storage and finally equilibrated to the pH of sigumjang, 5.5, on day 14. The amino-type nitrogen content of SMPL increased linearly during the marination period. Due to the lower extractability and higher pH compared to the control, the volume of myofibrillar fragments in SMPL decreased during the marination period. SMPL showed an increase in free amino acids related to umami (Asp and Glu) and sweet (Ser, Thr, Ala and Gly) tastes compared to the control. These may indicate improvement of sensory qualities of SMPL. The results also provide valuable information for the use of sigumjang in the development of novel meat products.

Fermented barley extracts with Lactobacillus plantarum dy-1 decreased fat accumulation of Caenorhabditis elegans in a daf-2-dependent mechanism.

Barley, a kind of cereal, is rich in polysaccharides, phenols, proteins, ß-glucan, etc. Our previous studies discovered that extracts from Lactobacillus plantarum dy-1-fermented barley (LFBE) held strong anti-obesity property in obese rats through inhibiting inflammation and suppressing the differentiation in 3T3-L1 preadipocytes; however, the precise mechanism of LFBE regulating lipid metabolism remains elusive. Results suggested LFBE and its main active components, especially the total phenols, exhibited fat-lowering effects in glucose treated Caenorhabditis elegans at a certain concentration. Additionally, LFBE and the main components changed related genes in the insulin signaling pathway, fatty acid oxidation, and synthesis. Following verification study using mutants confirmed that the daf-2 gene rather than the daf-16 gene was required in LFBE and main components regulating lipid metabolism, which also involved in the process of fatty acid ß-oxidation and unsaturated fatty acid synthesis. Results demonstrated that LFBE and its main bioactivate compounds inhibited fat accumulation partly in a daf-2-dependent mechanism. PRACTICAL APPLICATIONS: Our previous studies have reported that extracts of fermented barley exhibited anti-obesity activity. However, little is known about which functional factors play a leading role in decreasing fat deposition and its precise mechanism. Results indicated that daf-2 mediated signaling pathways involved in the fat-lowering effects of LFBE and its main components. Our findings are beneficial to understand the main nutritional ingredients in LFBE which are ideal and expected in functional foods for the obese.

Effect of Lactobacillus plantarum fermented barley on plasma glycolipids and insulin sensitivity in subjects with metabolic syndrome.

Fermented barley (FB) flour by Lactobacillus plantarum is richer in dietary fiber, polyphenols, gamma-aminobutyric acid, and other biologically active ingredients. This study aimed to determine the impacts of fermented barley - wheat flour compound noodle (FBWN) on glucose and fat metabolism in subjects with metabolic syndrome. This was a single-blinded and parallel 10-week clinical trial study. Subjects were randomly assigned into the trial group (FBWN) and whole wheat noodles group (WWN), and were measured on the beginning of week 3 and the ending of week 10. The glucose level at 30 and 60 min was significantly decreased after FBWN intervention. Levels of fasting blood glucose, HbA1c, and TG were all declined after FBWN intervention compared to before in the trial group. Moreover, the fat mass, fat rate, and visceral fat were decreased by 6.48, 7.19, 6.3 kg after FBWN intervention, respectively, while muscle mass and basal metabolic rate rose 7.44 kg and 252.60 kcal. PRACTICAL APPLICATIONS: Many studies have illustrated that the extraction of fermented barley held the activities of anti-obesity, antitumor, and so on. Moreover, this present study evaluated the effects of fermented barley by Lactobacillus plantarum on patients with metabolic syndrome. Results indicated that FB benefits the subjects on improving plasma glycolipids and insulin sensitivity, decreasing visceral fat level, and increasing satiety. The findings showed that the products of FB may be beneficial to dietary manipulations, thus, reducing the burden of patients.

Signaling pathways associated with macrophage-activating polysaccharides purified from fermented barley.

Barley is commonly used in many food and health products. We have previously demonstrated the macrophage-stimulating properties of polysaccharides derived from fermented barley. In this study, three polysaccharide fractions (BF-I-III) were purified from fermented barley and their monosaccharide composition was analyzed. Their immune-stimulatory activities and intracellular signaling pathways were also studied in RAW264.7 cells. Among the three fractions, BF-I exhibited enhanced macrophage activation properties, such as inducing the production of IL-6, IL-12, and TNF-α. However, BF-II and BF-III showed moderate effects on RAW 264.7 cells. BF-I treatment led to the phosphorylation of MAPKs, NF-κB, and c-Jun (major component of AP-1 transcription factor) and induced the nuclear translocation of p65 in RAW264.7 cells. In addition, experiments with neutralizing antibodies showed that Dectin-1, toll-like receptor (TLR) 4, scavenge receptor (SR), and CD14 were mainly involved in the stimulation of nitric oxide (NO) production by BF-I which was suppressed by the inhibition of JNK phosphorylation. These findings suggest that BF-I, isolated from fermented barley, has an immune potentiation activity on macrophages, where it activates the JNK signaling pathway via several macrophage receptors including dectin-1, TLR4, SR, and CD14.

Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism.

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION: These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.

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.

Protective effects of a triple-fermented barley extract (FBe) against HCl/EtOH-induced gastric mucosa damage in mice.

This study was designed to observe the possible protective effects of a triple-fermented barley (Hordeum vulgare L.) extract (FBe) obtained by saccharification and using Saccharomyces cerevisiae and Weissella cibaria in alleviating gastric damage induced by a hydrochloric acid (HCl) and ethanol (EtOH) mixture in mice. After oral administration of FBe (300, 200, and 100 mg/kg) followed by 1 hr before and after the single treatment of HCl/EtOH (H/E) mixture, the hemorrhagic lesion scores, histopathology of the stomach, gastric nitrate/nitrite content, lipid peroxidation, and antioxidant defense systems including catalase and superoxide dismutase activities were observed. Following a single oral treatment of H/E-induced gastric damages as measured by hemorrhagic gross lesions and histopathological gastric, ulcerative lesions were significantly and dose-dependently (p < 0.01 or p < 0.05) inhibited in mice, when all three different doses of FBe were administered as compared to those in H/E control mice. In particular, FBe also increased gastric nitrate/nitrite content and strengthened the antioxidant defense, with a decrease in the level of gastric lipid peroxidation, but increased the activities of CAT and SOD. Moreover, the effects of FBe are comparable to that of ranitidine, a reference drug. The obtained results suggest that this fermented barley extract prevented mice from H/E-induced gastric mucosal damages through the suppression of inflammatory responses and oxidative stress-responsive free radicals. Thus, FBe can be useful to treat patients suffering from gastric mucosal disorders as a potent food supplement, and thereby, it would increase the necessity of application in the food industry.

Sigumjang (fermented barley bran) water-soluble extracts inhibit the expression of adipogenic and lipogenic regulators in 3T3-L1 adipocytes.

Sigumjang prepared from fermented barley bran is a traditional fermented food found only in the Gyeongsang-do area of South Korea. There have been no studies reported to date despite the potential bioactivities of sigumjang. In this study, the anti-obesity activities of sigumjang extracts (SEs) during 3T3-L1 differentiation into adipocytes were investigated. SEs inhibited adipocyte differentiation by suppressing the CCAAT/enhancer binding protein-ß and sterol regulatory element binding protein-1c expression in the early stage of differentiation, followed by the suppression of the peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein-α, and adiponectin. These changes in adipogenic markers induced inhibition of lipogenesis via down-regulation of mainly fatty acid synthase, acetyl-CoA carboxylase, fatty acid binding protein 4, and perilipin. These results were more significant in the extract of sigumjang fermented with isolated Bacillus amyloliquefaciens MFST compared to naturally fermented sigumjang group. SEs can be considered as a useful material for developing food with health benefits and anti-obesity properties.

Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats.@*METHODS@#In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw).@*RESULTS@#In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity.@*CONCLUSION@#These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.

Fermented Barley Extracts with Lactobacillus plantarum dy-1 Rich in Vanillic Acid Modulate Glucose Consumption in Human HepG2 Cells / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effect of fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) for modulating glucose consumption in HepG2 cells via miR-212 regulation.</p><p><b>METHODS</b>Hepatocellular carcinoma (HepG2) cells were treated with palmitate. After 12 h, palmitate-induced HepG2 cells were treated with LFBE and its main components. Changes in glucose consumption, proinflammatory cytokine secretion, and miRNA-212 expression in HepG2 cells was observed.</p><p><b>RESULTS</b>Treatment with LFBE rich in vanillic acid (VA) increased glucose consumption and reduced proinflammatory cytokine secretion in HepG2 cells. LFBE and VA normalized the upregulation of miR-212, which led to the upregulation of dual-specificity phosphatase-9 (DUSP9), a direct target of miR-212, at both protein and mRNA levels. Downregulation of miR-212 markedly increased glucose consumption and reduced proinflammatory cytokine secretion by enhancing DUSP9 expression.</p><p><b>CONCLUSION</b>The results showed the benefit of LFBE and miR-212 downregulation in modulating glucose consumption and reducing proinflammatory cytokine secretion by targeting DUSP9. VA in LFBE was a strong regulator of palmitate-induced abnormal glucose consumption in HepG2 cells and can be a primary mediator.</p>