Intestinal microbiomics and liver metabolomics insights into the preventive effects of chromium (III)-enriched yeast on hyperlipidemia and hyperglycemia induced by high-fat and high-fructose diet.

In recent years, organic chromium (III) supplements have received increasing attentions for their low toxicity, high bioavailability and wide range of health-promoting benefits. This study aimed to investigate the preventive effects of chromium (III)-enriched yeast (YCr) on high-fat and high-fructose diet (HFHFD)-induced hyperlipidemia and hyperglycemia in mice, and further clarify its mechanism of action from the perspective of intestinal microbiomics and liver metabolomics. The results indicated that oral administration of YCr remarkably inhibited the aberrant elevations of body weight, blood glucose and lipid levels, hepatic cholesterol (TC) and triglyceride (TG) levels caused by HFHFD. Liver histological examination showed that oral YCr intervention inhibited HFHFD induced liver lipid accumulation. Besides, 16S rDNA amplicon sequencing showed that YCr intervention was beneficial to ameliorating intestinal microbiota dysbiosis by altering the proportion of some intestinal microbial phylotypes. Correlation-based network analysis indicated that the key intestinal microbial phylotypes intervened by YCr were closely related to some biochemical parameters associated with glucose and lipid metabolism. Liver metabolomics analysis revealed that dietary YCr intervention significantly regulated the levels of some biomarkers involved in purine metabolism, glycerophospholipid metabolism, citrate cycle, pyrimidine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and so on. Moreover, dietary YCr intervention regulated the mRNA levels of key genes associated with glucose, cholesterol, fatty acids and bile acids metabolism in liver. These findings suggest that dietary YCr intervention has beneficial effects on glucose and lipid metabolism by regulating intestinal microbiota and liver metabolic pathway, and thus can be served as a functional component to prevent hyperlipidemia and hyperglycemia.

Organic chromium derived from the chelation of Ganoderma lucidum polysaccharide and chromium (III) alleviates metabolic syndromes and intestinal microbiota dysbiosis induced by high-fat and high-fructose diet.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Corrigendum to "Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake" [Curr. Res. Food Sci. 5(2022) 515-530].

[This corrects the article DOI: 10.1016/j.crfs.2022.02.013.].

Evaluation of Volatile Profile and In Vitro Antioxidant Activity of Fermented Green Tea Infusion With Pleurotus sajor-caju (Oyster Mushroom).

Green tea has distinct astringency, bitter taste, and typical green flavor because of its post-harvest treatment without withering and enzymatic oxidation. Microbial fermentation has been identified as a promising strategy that could give green tea infusion a special taste flavor. This might be linked to the metabolic transformation ability of microorganisms. In this study, starter culture of edible mushroom Pleurotus sajor-caju (oyster mushroom) was used for submerged fermentation of green tea infusion in order to improve its flavor and taste quality. The volatile profile determined by headspace solid-phase microextraction, coupled with gas chromatography mass spectrometry, showed that the contents of (Z)-2-penten-1-ol and methyl heptadienone in green tea infusion were decreased significantly by the fermentation with the basidiomycete P. sajor-caju (p < 0.01), which would alleviate the herbal and grass flavor of green tea infusion to a certain extent. Meanwhile, the contents of linalool and geraniol were increased 9.3 and 11.3 times, respectively, whereas methyl salicylate was newly produced after fermentation by P. sajor-caju, endowing the fermented tea infusion with a pleasant flower and fruit aroma. In addition, the polyphenol profile was determined using high-performance liquid chromatography equipped with ion trap mass spectrometry, and the results indicated that the contents of most polyphenols in green tea infusion decreased significantly after fermentation by P. sajor-caju. The reduction of catechins and anthocyanins in fermented green tea infusion alleviated the astringency and bitterness. Moreover, the antioxidant activity of fermented green tea infusion was obviously decreased, especially the DPPH-free radical-scavenging ability and the ferric-reducing power. However, it is noteworthy that the ABTS-free radical scavenging ability was improved compared with the unfermented one, indicating that the increased tea pigments and volatile metabolites (such as linalool and geraniol) after fermentation with P. sajor-caju may also contribute to the antioxidant capacity of fermented green tea infusion. Overall, the innovative approach driven by P. sajor-caju fermentation has achieved promising potential to manipulate the green tea flavor.

Ganoderic acid A from Ganoderma lucidum protects against alcoholic liver injury through ameliorating the lipid metabolism and modulating the intestinal microbial composition.

Alcoholic liver injury is mainly caused by long-term excessive alcohol consumption and has become a global public threat to human health. It is well known that Ganoderma lucidum has excellent beneficial effects on liver function and lipid metabolism. The object of this study was to investigate the hepatoprotective effects of ganoderic acid A (GAA, one of the main triterpenoids in G. lucidum) against alcohol-induced liver injury and reveal the underlying mechanisms of its protective effects. The results showed that oral administration of GAA significantly inhibited the abnormal elevation of the liver index, serum total triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice exposed to alcohol intake, and also significantly protected the liver against alcohol-induced excessive lipid accumulation and pathological changes. Besides, alcohol-induced oxidative stress in the liver was significantly ameliorated by the dietary intervention of GAA through decreasing the hepatic levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA), and increasing hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and hepatic levels of glutathione (GSH). In addition, GAA intervention evidently ameliorated intestinal microbial disorder by markedly increasing the abundance of Muribaculaceae, Prevotellaceae, Jeotgalicoccus, Bilophila, Family_XIII_UCG_001, Aerococcus, Ruminococcaceae_UCG_005, Harryflintia, Christensenellaceae, Rumonpcpccaceae, Prevotelaceae_UCG_001, Clostridiales_vadinBB60_group, Parasutterella and Bifidobacterium, but decreasing the proportion of Lactobacillus, Burkholderia_Caballeroria_Paraburkholderia, Escherichia_Shigella and Erysipelatoclostridium. Furthermore, liver metabolomics based on UPLC-QTOF/MS demonstrated that oral administration of GAA had a significant regulatory effect on the composition of liver metabolites in mice exposed to alcohol intake, especially the levels of the biomarkers involved in the metabolic pathways of riboflavin metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, fructose and mannose metabolism. Moreover, dietary supplementation of GAA significantly regulated the hepatic mRNA levels of lipid metabolism and inflammatory response related genes. Conclusively, these findings demonstrate that GAA has beneficial effects on alleviating alcohol-induced liver injury and is expected to become a new functional food ingredient for the prevention of alcoholic liver injury.

Pediococcus acidilactici FZU106 alleviates high-fat diet-induced lipid metabolism disorder in association with the modulation of intestinal microbiota in hyperlipidemic rats.

Probiotics have been proved to have beneficial effects in improving hyperlipidemia. The purpose of the current research was to investigate the ameliorative effects of Pediococcus acidilactici FZU106, isolated from the traditional brewing of Hongqu rice wine, on lipid metabolism and intestinal microbiota in high-fat diet (HFD)-induced hyperlipidemic rats. Results showed that P. acidilactici FZU106 intervention obviously inhibited the abnormal increase of body weight, ameliorated serum and liver biochemical parameters related to lipid metabolism and oxidative stress. Histopathological evaluation also showed that P. acidilactici FZU106 could significantly reduce the excessive lipid accumulation in liver caused by HFD-feeding. Furthermore, P. acidilactici FZU106 intervention significantly increased the short-chain fatty acids (SCFAs) levels in HFD-fed rats, which was closely related to the changes of intestinal microbial composition and metabolism. Intestinal microbiota profiling by high-throughput sequencing demonstrated that P. acidilactici FZU106 intervention evidently increased the proportion of Butyricicoccus, Pediococcus, Rothia, Globicatella and [Eubacterium]_coprostanoligenes_group, and decreased the proportion of Corynebacterium_1, Psychrobacter, Oscillospira, Facklamia, Pseudogracilibacillus, Clostridium_innocuum_group, Enteractinococcus and Erysipelothrix in HFD-fed rats. Additionally, P. acidilactici FZU106 significantly regulated the mRNA levels of liver genes (including CD36, CYP7A1, SREBP-1c, BSEP, LDLr and HMGCR) involved in lipid metabolism and bile acid homeostasis. Therefore, these findings support the possibility that P. acidilactici FZU106 has the potential to reduce the disturbance of lipid metabolism by regulating intestinal microflora and liver gene expression profiles.

Ganoderic acids-rich ethanol extract from Ganoderma lucidum protects against alcoholic liver injury and modulates intestinal microbiota in mice with excessive alcohol intake.

Alcoholic liver injury is mainly caused by excessive alcohol consumption and has become a global public health problem threatening human health. It is well known that Ganoderma lucidum possesses various excellent beneficial effects on liver function and lipid metabolism. The purpose of this study was to evaluate the underlying protective effect and action mechanism of ganoderic acids-rich G. lucidum ethanol extract (GLE) on alcohol-induced liver injury in mice with excessive alcohol intake. Results showed that oral administration of GLE could obviously inhibit the abnormal increases of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and also significantly protect the liver against alcohol-induced excessive hepatic lipid accumulation and pathological changes. In addition, alcohol-induced oxidative stress in liver was significantly ameliorated by the dietary intervention of GLE through reducing the hepatic levels of maleic dialdehyde (MDA) and lactate dehydrogenase (LDH), and increasing the hepatic levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and alcohol dehydrogenase (ADH). Compared with the model group, GLE intervention significantly ameliorated the intestinal microbial disorder by elevating the relative abundance of Ruminiclostridium_9, Prevotellaceae_UCG-001, Oscillibacter, [Eubacterium]_xylanophilum_group, norank_f_Clostridiates_vadinBB60_group, GCA-900066225, Bilophila, Ruminococcaceae_UCG-009, norank_f_Desulfovibrionaceae and Hydrogenoanaerobacterium, but decreasing the proportion of Clostridium_sensu_stricto_1. Furthermore, liver metabolomic profiling suggested that GLE intervention had a significant regulatory effect on the composition of liver metabolites in mice with excessive alcohol intake, especially the levels of some biomarkers involved in primary bile acid biosynthesis, riboflavin metabolism, tryptophan metabolism, biosynthesis of unsaturated fatty acids, fructose and mannose metabolism, glycolysis/gluconeogenesis. Additionally, dietary supplementation with GLE significantly regulated the mRNA levels of key genes related to fatty acids metabolism, ethanol catabolism and inflammatory response in liver. Conclusively, these findings indicate that GLE has a potentially beneficial effect on alleviating alcohol-induced liver injury and may be developed as a promising functional food ingredient.

The Meridian Tropism and Classification of Red Yeast Rice Investigated by Monitoring Dermal Electrical Potential.

Red yeast rice is a traditional Chinese medicine and food that has been purported to color food, ferment, and lower cholesterol. In order to study the antioxidative capacity of red yeast rice and the effects on electrical potential difference (EPD) of 12 acupuncture meridians, the pH value, oxidation reduction potential (ORP), ABTS, FRAP, T-SOD, and particle size distribution of red yeast rice were analyzed. 20 volunteers were recruited and randomly divided into two groups, the red yeast rice group (10 g red yeast rice and 40 g water) and control CK group (50 g water). The left 12 acupuncture meridians' EPD was real-time monitored. Samples were taken at the 10th minutes. The whole procedure continued for 70 minutes. It is shown that the pH value of the red yeast rice was 4.22, the ORP was 359.63 mV, the ABTS was 0.48 mmol Trolox, the FRAP was 0.08 mmol FeSO4, the T-SOD was 4.71 U, and the average particle size was 108 nm (7.1%) and 398.1 nm (92.9%). The results of 12 acupuncture meridians' EPD showed that the red yeast rice can significantly affect the EPD of stomach, heart, small intestine, and liver meridians.

The beneficial effects of Lactobacillus brevis FZU0713-fermented Laminaria japonica on lipid metabolism and intestinal microbiota in hyperlipidemic rats fed with a high-fat diet.

This study aimed to investigate the beneficial effects of the oral administration of Lactobacillus brevis FZU0713-fermented Laminaria japonica (FLJ) on lipid metabolism and intestinal microbiota in hyperlipidemic rats fed with a high-fat diet (HFD). The results demonstrated that the oral administration of FLJ significantly inhibited obesity and improved the serum and hepatic biochemical parameters in HFD-fed rats. Histopathological results also indicated that FLJ intervention could significantly reduce the accumulation of lipid droplets in the liver induced by HFD feeding. Furthermore, FLJ intervention up-regulated the fecal short-chain fatty acid (SCFA) levels (mainly acetate, propionate and isobutyrate) in HFD-fed rats. Intestinal microbiota profiling by 16S rRNA gene sequencing revealed that FLJ intervention increased the relative abundance of Akkermansia, Collinsella, Ruminococcaceae_UCG-013, Defluviitaleaceae_UCG-011, Intestinimonas, Actinomyces and Tyzzerella, but decreased the abundance of Flavonifractor, Collinsella, Sporosarcina and Lacticigenium. Based on Spearman's correlation, the fecal levels of TC, TG, acetic acid and butyric acid were positively correlated with the relative abundance of Akkermansia and Ruminococcaceae_NK4A214, but negatively correlated with the relative amount of Flavonifractor and Collinsella. The metabolic function of intestinal microbiota predicted by PICRUSt analysis of 16S rRNA gene sequences demonstrated that primary and secondary bile acid biosyntheses, fatty acid biosynthesis, taurine and hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, etc. were significantly down-regulated after 8 weeks of FLJ intervention. Additionally, FLJ intervention significantly regulated the hepatic mRNA levels (including BSEP, CYP7A1, LDLR, HMGCR, CD36 and SREBP1-C) involved in lipid metabolism and bile acid homeostasis. In conclusion, these findings support the possibility that Laminaria japonica fermented with probiotic Lactobacillus has the potential to reduce the disturbance of lipid metabolism by regulating intestinal microflora and liver gene expression profiles, so it can be employed as a potential functional food to prevent hyperlipidemia.

Potential mechanisms underlying the ameliorative effect of Lactobacillus paracasei FZU103 on the lipid metabolism in hyperlipidemic mice fed a high-fat diet.

Lactobacillus paracasei FZU103, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorder of lipid metabolism. This study aimed to determine the beneficial effects of L. paracasei FZU103 on improving hepatic lipid accumulation associated with hyperlipidemia. Results indicated that L. paracasei FZU103 intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation oflipid dropletsin the livers induced by HFD-feeding was greatly alleviated by L. paracasei FZU103 intervention. In addition, L. paracasei FZU103 also promoted the excretion of bile acids (BAs) through feces. Metagenomic analysis revealed that oral supplementation with L. paracasei FZU103 significantly increased the relative abundance of Ruminococcus, Alistipes, Pseudoflavonifractor and Helicobacter, but decreased the levels of Blautia, Staphylococcos and Tannerella in HFD-fed mice. The relationships between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by correlation heatmap and network. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. paracasei FZU103 had a significant regulatory effect on the metabolic pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, unsaturated fatty acids biosynthesis, riboflavin metabolism, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Additionally, L. paracasei FZU103 intervention regulated expression of hepatic genes involved in lipid metabolism and bile acid homeostasis, and promoted fecal excretion of intestinal BAs. These findings present new evidence supporting that L. paracasei FZU103 has the potential to improve lipid metabolism, and could be used as a potential functional food for the prevention of hyperlipidemia.

Monascus purpureus-fermented common buckwheat protects against dyslipidemia and non-alcoholic fatty liver disease through the regulation of liver metabolome and intestinal microbiome.

Monascus-fermented rice has been used to treat digestive disorder and promote blood circulation in China and other Asian countries for centuries. However, the effects and mechanisms of Monascus purpureus-fermented common buckwheat (HQ) on non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are unclear. Here, oral supplementation of HQ significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated some biochemical parameters of serum and liver related to lipid metabolism in mice fed a high-fat and high-cholesterol diet (HFD). Histological analysis also showed that the excessive accumulation of lipid droplets in the livers induced by HFD-feeding was greatly alleviated by HQ supplementation. Metagenomic analysis revealed that HQ supplementation made significant structural changes in the intestinal microflora of mice fed with HFD. The Spearman's correlation analysis revealed that physiological index, serum and liver lipid profiles were positively correlated with Bacteroidales S24-7, Streptococcus, Allobaculum, and Clostridiales XIII, but negatively associated with Lactobacillus, Ruminococcaceae_NK4A214 group, Ruminiclostridium, and Alistipes. UPLC-QTOF/MS-based liver metabolomics demonstrated that HQ intervention had significant regulatory effects on the metabolic pathways of primary bile acid biosynthesis, pyrimidine metabolism, ether lipid metabolism, glutathione metabolism, glycine, serine and threonine metabolism, and amino sugar and nucleotide sugar metabolism, etc. Additionally, HQ intervention regulated the mRNA levels of hepatic genes involved in hepatic lipid metabolism and bile acid homeostasis. Collectively, these findings present new evidence supporting that HQ has the potential to ameliorate dyslipidemia and NAFLD via modulating the intestinal microbial populations and hepatic metabolite profile in hyperlipidemic mice induced by HFD.

Ganoderic acid A from Ganoderma lucidum ameliorates lipid metabolism and alters gut microbiota composition in hyperlipidemic mice fed a high-fat diet.

Ganoderic acid A (GA) is one of the most abundant triterpenoids in Ganoderma lucidum, and has been proved to possess a wide range of beneficial health effects. The aim of the current study is to investigate the amelioration effects and mechanism of GA on improving hyperlipidemia in mice fed a high-fat diet (HFD). The results showed that GA intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, and ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation of lipid droplets in the liver induced by HFD-feeding was greatly alleviated by GA intervention. In addition, GA intervention also increased the level of short chain fatty acids (SCFAs) in the intestine and promoted the excretion of bile acids (BAs) through feces. High-throughput sequencing of bacterial full-length 16S rDNA revealed that daily supplementation with GA made significant structural changes in the gut microbial population of mice fed with HFD, in particular modulating the relative abundance of some function related microbial phylotypes. The relationships between lipid metabolic parameters and gut microbial phylotypes were also revealed by correlation analysis based on a heatmap and network. The result showed that 46 key gut microbial phylotypes (OTUs) were markedly correlated with at least one lipid metabolic parameter. Moreover, UPLC-QTOF/MS-based liver metabolomics showed that 111 biomarkers (47 up-regulated metabolites and 64 down-regulated metabolites) were significantly changed after high-dose GA intervention (75 mg kg-1 day-1), compared with the HFD-fed hyperlipidemic mice. Metabolic pathway enrichment analysis of the differential hepatic metabolites demonstrated that GA intervention had significant regulatory effects on primary bile acid biosynthesis, fatty acid biosynthesis, amino sugar and nucleotide sugar metabolism, inositol phosphate metabolism, and so on. In addition, GA intervention regulated the mRNA levels of hepatic genes involved in fatty acid metabolism and bile acid homeostasis. These findings present new evidence supporting that GA from G. lucidum has the potential to alleviate lipid metabolic disorders and ameliorate the imbalance of gut microflora in a positive way.

Protective Mechanism of Common Buckwheat (Fagopyrum esculentum Moench.) against Nonalcoholic Fatty Liver Disease Associated with Dyslipidemia in Mice Fed a High-Fat and High-Cholesterol Diet.

This study aimed to investigate the protective mechanism of common buckwheat (Fagopyrum esculentum Moench.) against nonalcoholic fatty liver disease (NAFLD) associated with dyslipidemia in mice that were fed a high-fat and high-cholesterol diet (HFD). Results showed that oral supplementation of common buckwheat significantly improved physiological indexes and biochemical parameters related to dyslipidemia and NAFLD in mice fed with HFD. Furthermore, the HFD-induced reductions in fecal short-chain fatty acids were reversed by common buckwheat intervention, which also increased the fecal bile acid (BA) abundance compared with HFD-induced hyperlipidemic mice. Liver metabolomics based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry demonstrated that common buckwheat supplementation made significant regulatory effects on the pentose phosphate pathway, starch and sucrose metabolism, primary BA biosynthesis, and so forth. The results of high-throughput sequencing revealed that common buckwheat supplementation significantly altered the structure of the intestinal microbiota in mice fed with HFD. The correlations between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by the heatmap and network. Additionally, common buckwheat intervention regulated the mRNA expressions of genes responsible for liver lipid metabolism and BA homeostasis, thus promoting BA synthesis and excretion. These findings confirmed that common buckwheat has the outstanding ability of improving lipid metabolism and could be used as a potential functional food for the prevention of NAFLD and hyperlipidemia.

The protective mechanism of Lactobacillus plantarum FZU3013 against non-alcoholic fatty liver associated with hyperlipidemia in mice fed a high-fat diet.

Lactobacillus plantarum FZU3013, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorders of lipid metabolism. This study aimed to investigate the role of L. plantarum FZU3013 in improving non-alcoholic fatty liver (NAFL) associated with hyperlipidemia in mice fed a high-fat diet. The results indicated that L. plantarum FZU3013 intervention significantly reduced the HFD-induced body weight gain and the abnormal levels of serum total triglycerides (TG), total cholesterol (TC) and low-density lipoprotein (LDL-C), and inhibited the excessive accumulation of liver lipids. In addition, L. plantarum FZU3013 also promoted the excretion of bile acids through feces. Metagenomic and multivariate statistical analysis revealed that L. plantarum FZU3013 made significant structural changes in the intestinal microbiome of the mice fed with HFD, in particular by modulating the relative abundance of some function related microbial phylotypes. Furthermore, ultra-performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. plantarum FZU3013 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic mice, especially on the levels of some important biomarkers involved in the pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Moreover, L. plantarum FZU3013 regulated the mRNA expression levels of the genes responsible for liver lipid and cholesterol metabolism. L. plantarum FZU3013 intervention increased the hepatic mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and the bile salt export pump (BSEP), suggesting enhanced bile acid synthesis and excretion from the liver. These findings present new evidence supporting that L. plantarum FZU3013 has the potential to improve lipid metabolism disorders through modulating specific intestinal microbial phylotypes and regulating hepatic lipid metabolism related genes, therefore it could be used as a potential functional food for the prevention of NAFL and hyperlipidemia.

The protective mechanisms of macroalgae Laminaria japonica consumption against lipid metabolism disorders in high-fat diet-induced hyperlipidemic rats.

Macroalgae Laminaria japonica (MLJ) has been reported to exhibit various biological activities including improving immunity, anti-aging, anti-tumor, anti-atherosclerosis and anti-diabetic, but the protective mechanisms of MLJ consumption against non-alcoholic fatty liver disease (NAFLD) associated with hyperlipidemia remain poorly understood. This study demonstrated that MLJ consumption prevented high-fat diet (HFD)-induced NAFLD associated with hyperlipidemia in a rat model, and improved hyperlipidemia-related parameters, e.g. serum and hepatic lipid profiles. Moreover, histological analysis showed that MLJ reduced lipid deposition in adipocytes and hepatocytes compared with the HFD group. Such beneficial effects may be associated with the modulation of the intestinal microbiota, especially some key microbial phylotypes involved in lipid metabolism homeostasis. The underlying protective mechanisms of MLJ consumption against HFD-induced NAFLD associated with hyperlipidemia were also studied by ultra-high performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics coupled with pathway analysis. The metabolic pathway enrichment analysis of the differentially abundant hepatic metabolites indicated that primary bile acid biosynthesis metabolism and cysteine and methionine metabolism were the two main metabolic pathways altered by MLJ consumption when compared with the model group. The analysis of the transcription levels of liver-related genes by RT-qPCR and the expressions of liver-related proteins by immunohistochemistry (IHC) showed that MLJ consumption could regulate the levels of mRNA transcription and protein expression related to hepatic lipid metabolism. In short, this study indicates that MLJ could be developed as functional food supplement for the prevention or treatment of NAFLD associated with hyperlipidemia.

Comparative transcriptomic analysis reveals the regulatory effects of inorganic nitrogen on the biosynthesis of Monascus pigments and citrinin.

Monascus spp. and its secondary metabolites have been widely applied in foods and medicines for thousands of years in eastern Asia. Nitrogen sources are essential nutrients for the growth and metabolism of Monascus spp. Our previous study found that inorganic nitrogen sources (especially NH4Cl and NH4NO3) promoted the biosynthesis of Monascus pigments (MPs) and inhibited the production of citrinin. The objective of the present study was to investigate the regulatory mechanism of inorganic nitrogen on the biosynthesis of MPs and citrinin by the comparative transcriptional approach (RNA sequencing combined with RT-qPCR). Results indicated that the submerged fermentation of M. purpureus M3103 with NH4Cl or NH4NO3 as the sole nitrogen source can significantly increase the yields of MPs (especially for Monascus orange and red pigments) and decrease citrinin production, compared with the organic nitrogen source (peptone group). Comparative transcriptomic profiling by RNA sequencing found that the numbers of differentially expressed genes (DEGs) between different experimental groups-M group (peptone group) vs. ML group (NH4Cl group), and M group (peptone group) vs. MX group (NH4NO3 group), were 722 and 1287, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that genes involved in carbon and nitrogen metabolism, biosynthesis of amino acids were up-regulated by NH4Cl and NH4NO3, which would produce more biosynthetic precursors for MPs. Whereas, the inorganic nitrogen source (both of NH4Cl and NH4NO3) down-regulated the expression levels of genes involved in tyrosine metabolism. In addition, NR analysis indicated that the essential genes and transcription factors involved in the biosynthesis pathway of citrinin were down-regulated by NH4Cl and NH4NO3. These results indicated that NH4Cl or NH4NO3 as a nitrogen source for M. purpureus M3103 can significantly promote the precursor synthesis of Monascus pigments, but reduce the transcription of polyketide synthase for citrinin, and therefore significantly increase Monascus pigments production and decrease citrinin formation. These findings will facilitate a comprehensive understanding of the regulatory mechanisms of inorganic nitrogen in the biosynthesis of secondary metabolites in M. purpureus, and would benefit the application of M. purpureus in the production of MPs.

Effects of TAT-SOD at Acupoints on Essential Hypertension by Monitoring Meridians Electrical Potential.

OBJECTIVES: To investigate the effect on essential hypertension of the topical application of TAT-Cu, Zn-superoxide dismutase (TAT-SOD) at left acupoint Zusanli (ST 36), and to observe whether the change of electrical potential difference (EPD) can be related to the change of blood pressure. METHODS: Sixteen patients with essential hypertension and 16 healthy subjects were included in the study. EPD between the left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) was firstly screened out for the EPD detection. An intracellular superoxide quenching enzyme, TAT-SOD, was topically applied to the acupoint ST 36 within an area of 1 cm2 once a day, and the influence on EPD was investigated. The dosage applied to TAT-SOD group (n=8) was 0.2 mL of 3000 U/mL TAT-SOD cream prepared by adding purified TAT-SOD to a vehicle cream, while placebo group (n=8) used the vehicle cream instead. The left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) were selected for EPD measurement after comparing EPD readings between 5 acupoints on each of all 12 meridians. RESULTS: EPDs between the left acupoints of GB 34 and GB 40 for 16 patients of essential hypertension and 16 healthy subjects were 44.9±6.4 and 5.6±0.9 mV, respectively. Daily application of TAT-SOD for 15 days at ST 36 of essential hypertension patients significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 179.6 and 81.5 mm Hg to 153.1 and 74.1 mm Hg, respectively. Responding to the change in blood pressure, EPD between the left acupoints of GB 34 and GB 40 also declined from 44.4 to 22.8 mV with the same trend. No change was observed with SBP, DBP and EPD between the left acupoints of GB 34 and GB 40 with the daily application of the placebo cream. CONCLUSION: Enzymatic scavenging of the intracellular superoxide at ST 36 proved to be effective in decreasing SBP and DBP. The results reconfirm the involvement of superoxide anions and its transportation along the meridians, and demonstrate that EPD between acupoints may be an indicator to reflect its functioning status. Moreover, preliminary results suggest a close correlation between EPD and blood pressure readings, implying a possibility of using EPD as a sensitive parameter for blood pressure and to monitor the effect of antihypertensive treatment.

Hypoglycemic and hypolipidemic mechanism of organic chromium derived from chelation of Grifola frondosa polysaccharide-chromium (III) and its modulation of intestinal microflora in high fat-diet and STZ-induced diabetic mice.

Polysaccharide from Grifola frondosa is an excellent metal-ion chelating agent owing to its distinctive structure and outstanding functional activities. Our previous research has successfully synthesized novel organic chromium derived from the chelation ofG. frondosapolysaccharide-chromium (III) [GFP-Cr(III)]. The purpose of present research was to reveal the hypoglycemic and hypolipidemic mechanism of GFP-Cr(III), and its relationship with the modulation of intestinal microflora. Successful fabrication of GFP-Cr(III) was verified by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and 1H NMR spectrum.The hypoglycemic and hypolipidemic effects were examined using type 2 diabetic mice induced by a high-fat diet (HFD) and streptozocin (STZ). Results indicated that GFP-Cr(III) intervention improved abnormal serum biochemical indicators (triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose), inhibited lipid accumulation and steatosis in the liver. Metagenomic analysis revealed that GFP-Cr(III) treatment produced obvious changes on the intestinal microflora in T2DM mice. Thecorrelationnetwork analysis further revealed that the serum and hepatic lipid profiles were positively correlated with Streptococcus and Enterococcus, but negatively correlated with Enterorhabdus, Ruminococcaceae-UCG-011, Coriobacteriaceae and Micrococcaceae. Meanwhile, oral administration with GFP-Cr(III) regulated the mRNA expression related to glucose and lipid metabolism. These results of present study suggest that GFP-Cr(III) could be used as potential functional food ingredients for the amelioration of hyperglycemia and hyperlipidemia.

Hypoglycemic and hypolipidemic activities of Grifola frondosa polysaccharides and their relationships with the modulation of intestinal microflora in diabetic mice induced by high-fat diet and streptozotocin.

This study aimed to investigate the hypoglycemic and hypolipidemic activities of polysaccharides from Grifola frondosa (GFP) in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ). Results showed that oral administration of GFP markedly reduced the serum levels of fasting blood glucose (FBG), oral glucose tolerance (OGT), cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and significantly decreased the hepatic levels of TC, TG and free fatty acids (FFA). Meanwhile, high-dose of GFP supplementation (900 mg/kg day) also showed powerful effects on moderating the composition of intestinal microflora in diabetic mice, especially altering the functionally relevant intestinal microbial phylotypes. Spearman's correlation network analysis revealed that key microbial phylotypes responding to GFP intervention were strongly correlated with the glucose and lipid metabolic disorders associated parameters. Moreover, GFP treatment regulated mRNA expression levels of the genes responsible for hepatic glucose and lipid metabolism. It is noteworthy that GFP treatment markedly increased mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acids (BAs) synthesis and excretion in liver. These findings demonstrated that GFP could prevent hyperglycemia and hyperlipidemia in diabetic mice by altering gut microbiota and regulating hepatic glycolipid metabolism related genes, and therefore could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.

Preparation of Ganoderma lucidum polysaccharide­chromium (III) complex and its hypoglycemic and hypolipidemic activities in high-fat and high-fructose diet-induced pre-diabetic mice.

Polysaccharide from Ganoderma lucidum is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel G. lucidum polysaccharide­chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ±â€¯1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were OH and CO groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a "blind zone" in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P < 0.01). More importantly, the GLP-Cr(III) complex had no significant adverse effects on the physiological metabolism, organ index, and liver tissue morphology of mice fed a normal diet. These results suggest that GLP-Cr(III) complex could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.