The modulation of Luffa cylindrica (L.) Roem supplementation on gene expression and amino acid profiles in liver for alleviating hepatic steatosis via gut microbiota in high-fat diet-fed mice: insight from hepatic transcriptome analysis.

Luffa cylindrica is a nutrient-dense vegetable with medical properties and can alleviate metabolic diseases. Numerous evidences demonstrated gut microbiota impacted the progress of nonalcoholic fatty liver disease (NAFLD). This study was to investigate the underlying mechanism of L. cylindrica supplementation against NALFD via gut microbiota from hepatic transcriptional and metabolic analysis. In diet-induced obese mice, we observed L. cylindrica supplementation (2 g/kg body weight) effectively alleviated high-fat diet-induced obese symptoms such as body weight, fat deposition, and insulin resistance. Notably, L. cylindrica supplementation significantly relieved hepatic steatosis and inflammation infiltration to decrease hepatic toxicity. RNA-sequencing analysis showed that 130 hepatic genes in total significantly altered responding to L. cylindrica supplementation. And signaling pathway analysis revealed that L. cylindrica supplementation down-regulated the transcriptional expressions of CD36 and Rxrg to inhibit hepatic lipid synthesis. Moreover, L. cylindrica supplementation increased the transcriptional expressions of Ass1, Cps1, Cth, Got1, Tat, and Gls2 to enhance amino acid levels (Gly, Ala, Pro, Val, Ile, Asn, Met, and Phe) and improve hepatic abnormal gluconeogenesis. Furthermore, in antibiotic-treated obese mice, L. cylindrica supplementation did not change these gene expressions along with the hepatic levels of lipid and amino acids. Taken together, L. cylindrica supplementation could effectively suppress hepatic steatosis in diet-induced obese mice through inhibiting lipid synthesis and enhancing amino acid levels in liver, which depended on gut microbiota. Thus, L. cylindrica might be one promising dietary supplementation targeting at gut microbiota to reduce NAFLD risk.

Zhang L ，Wang P ，Shi M ，Fang Z ，Ji J ，Liao X ，Hu X ，Chen F ... -  《-》

Gut microbiota determines the prevention effects of Luffa cylindrica (L.) Roem supplementation against obesity and associated metabolic disorders induced by high-fat diet.

Zhang L ，Shi M ，Ji J ，Hu X ，Chen F ... -  《-》

Dietary Luffa cylindrica (L.) Roem promotes branched-chain amino acid catabolism in the circulation system via gut microbiota in diet-induced obese mice.

High circulating branched-chain amino acid (BCAA) levels can be diagnosis indicators for obesity. Luffa cylindrica (luffa) is one of vegetables against obesity. However, whether the anti-obesity of luffa is associated with BCAA metabolism and gut microbiota remains unknown. Here, we used conventionally raised diet-induced obese (DIO) mice to prove dietary luffa could reduce higher circulating BCAA levels and upregulate the tissue-specific expressions of BCAA-catabolizing enzymes. Meanwhile, dietary luffa selectively decreased the relative abundances of g_Enterortabdus, g_Eubacterium_xylanophilum_group and g_Butyricicoccus that exhibited significantly positive correlations with BCAA levels, BMI and HOMA-IR. Bacterial functionality prediction indicated dietary luffa potentially inhibited bacterial BCAA biosynthesis for reducing BCAAs supplementation. More importantly, dietary luffa had no impacts on BCAA catabolism in germ-free-mimic DIO mice. Thus, dietary luffa improved BCAA dysfunction via gut microbiota to attenuate obesity. This study offers a novel insight into dietary intervention against obesity from the aspect of gut microbiota-amino acid metabolism.

Zhang L ，Yue Y ，Shi M ，Tian M ，Ji J ，Liao X ，Hu X ，Chen F ... -  《-》

Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis.

Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.

Wang P ，Wang J ，Li D ，Ke W ，Chen F ，Hu X ... -  《-》

Integrated omics analysis unraveled the microbiome-mediated effects of Yijin-Tang on hepatosteatosis and insulin resistance in obese mouse.

Gut microbiota play important roles in insulin homeostasis and the pathogenesis of non-alcoholic fatty liver diseases (NAFLD). Yijin-Tang (YJT), a traditional Korean and Chinese medicine, is used in the treatment of gastrointestinal diseases and obesity-related disorders such as insulin resistance (IR) and NAFLD. Our aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile. C57BL/6J mice were fed a normal chow diet (NC) or high-fat/high-cholesterol (HFHC) diet with or without YJT treatment. Hepatic lipid profiles were analyzed using liquid chromatography/mass spectrometry, and the composition of gut microbiota was investigated using 16S rRNA sequencing. Then, hepatic lipid profiles, gut microbiome, and inflammatory marker data were integrated using multivariate analysis and bioinformatics tools. YJT improved NAFLD, and 39 hepatic lipid metabolites were altered by YJT in a dose-dependent manner. YJT also altered the gut microbiome composition in HFHC-fed mice. In particular, Faecalibaculum rodentium and Bacteroides acidifaciens were altered by YJT in a dose-dependent manner. Also, we found significant correlation among hepatic phosphatidylglycerol metabolites, F. rodentium, and γδ-T cells. Moreover, interleukin (IL)-17, which is secreted by the γδ-T cell when it recognizes lipid antigens, were elevated in HFHC mice and decreased by YJT treatment. In addition, YJT increased the relative abundance of B. acidifaciens in NC or HFHC-fed mice, which is a gut microbiota that mediates anti-obesity and anti-diabetic effects by modulating the gut environment. We also confirmed that YJT ameliorated the gut tight junctions and increased short chain fatty acid (SCFA) levels in the intestine, which resulted in improved IR. These data demonstrated that gut microbiome and hepatic lipid profiles are regulated by YJT, which improved the IR and NAFLD in mice with diet-induced obesity.

Lee JE ，Lee SM ，Jung J 《-》