scholarly journals Gegen Qinlian Decoction Attenuates High-Fat Diet-Induced Steatohepatitis in Rats via Gut Microbiota

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Guo ◽  
Pang-hua Ding ◽  
Li-juan Liu ◽  
Lei Shi ◽  
Tang-you Mao ◽  
...  

Gut microbiota play an important role in modulating energy contribution, metabolism, and inflammation, and disruption of the microbiome population is closely associated with chronic metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD). Gegen Qinlian decoction (GGQLD), a well-known traditional Chinese herbal medicine (CHM), was previously found to regulate lipid metabolism and attenuate inflammation during NAFLD pathogenesis. However, the underlying mechanism of this process, as well as how the gut microbiome is involved, remains largely unknown. In this study, we investigated the effect of varying doses of GGQLD on the total amount and distribution of gut bacteria in rats fed a high-fat diet (HFD) for 8 weeks. Our analysis indicates that Oscillibacter and Ruminococcaceae_g_unclassified are the dominant families in the HFD group. Further, HFD-dependent differences at the phylum, class, and genus levels appear to lead to dysbiosis, characterized by an increase in the Firmicutes/Bacteroidetes ratio and a dramatic increase in the Oscillibacter genus compared to the control group. Treatment with GGQLD, especially the GGQLL dose, improved these HFD-induced changes in intestinal flora, leading to increased levels of Firmicutes, Clostridia, Lactobacillus, bacilli, and Erysipelotrichales that were similar to the controls. Taken together, our data highlight the efficacy of GGQLD in treating NAFLD and support its clinical use as a treatment for NAFLD/NASH patients.

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.


2021 ◽  
Author(s):  
Zhen Shi ◽  
Zhiyuan Fang ◽  
Xinxing Gao ◽  
Hao Yu ◽  
Yiwei Zhu ◽  
...  

Nuciferine (NF) has received extensive attention for its medicinal value in the treatment of metabolic diseases, such as obesity, but the effects of NF on obesity-related intestinal permeability, autophagy and...


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yan Yang ◽  
Wenting Zhang ◽  
Xiaohui Wu ◽  
Jing Wu ◽  
Chengjun Sun ◽  
...  

Objective. Our recent study demonstrated that growth differentiation factor 5 (GDF5) could promote white adipose tissue thermogenesis and alleviate high-fat diet- (HFD-) induced obesity in fatty acid-binding protein 4- (Fabp4-) GDF5 transgenic mice (TG). Here, we further investigated the effects of systemic overexpression of the GDF5 gene in adipocytes HFD-induced nonalcoholic fatty liver disease (NAFLD). Methods. Fabp4-GDF5 TG mice were administered an HFD feeding. NAFLD-related indicators associated with lipid metabolism and inflammation were measured. A GDF5 lentiviral vector was constructed, and the LO2 NAFLD cell model was induced by FFA solution (oleic acid and palmitic acid). The alterations in liver function, liver lipid metabolism, and related inflammatory indicators were analyzed. Results. The liver weight was significantly reduced in the TG group, which was in accordance with the significantly downregulated expression of TNFα, MCP1, Aim2, and SREBP-1c and significantly upregulated expression of CPT-1α and ACOX2 in TG mouse livers. Compared to that of cells in the FAA-free control group, LO2 cells with in situ overexpression of GDF5 developed lipid droplets after FFA treatment; the levels of triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly increased in both the GDF5 lentivirus and control lentivirus groups compared with those of the FAA-free group. Additionally, the levels of FAS, SREBP-1, CPT-1α, and inflammation-associated genes, such as ASC and NLRC4, were unaltered despite GDF5 treatment. Conclusion. Systemic overexpression of GDF5 in adipose tissue in vivo significantly reduced HFD-induced NAFLD liver damage in mice. The overexpression of GDF5 in hepatocytes failed to improve lipid accumulation and inflammation-related reactions induced by mixed fatty acids, suggesting that the protective effect of GDF5 in NAFLD was mainly due to the reduction in adipose tissue and improvements in metabolism. Hence, our study suggests that the management of NAFLD should be targeted to reduce the overall amount of body fat and improve metabolic status before the progression to nonalcoholic steatohepatitis occurs.


2020 ◽  
Vol 245 (6) ◽  
pp. 512-521 ◽  
Author(s):  
Xiangjie Qiu ◽  
Qiaona Ye ◽  
Mengxing Sun ◽  
Lili Wang ◽  
Yurong Tan ◽  
...  

Studies have shown that metabolic diseases, such as obesity, are significantly associated with intestinal flora imbalance. The amplification of opportunistic pathogens induced by the glyoxylic acid cycle contributes to intestinal flora imbalance. Promising, though, is that saturated hydrogen can effectively improve the occurrence and development of metabolic diseases, such as obesity. However, the specific mechanism of how saturated hydrogen operates is still not very clear. In this study, after a high-fat diet, the level of total cholesterol, total glyceride, and low-density lipoprotein in the peripheral blood of mice increased, and that of high-density lipoprotein decreased. Intestinal fatty acid metabolism-related gene Apolipoprotein E (ApoE), fatty acid synthase (FAS), intestinal fatty acid-binding protein (I-FAPB), acetyl-CoA carboxylase 1 (ACC1), peroxisome proliferator-activated receptor γ (PPARγ), and stearoyl-CoA desaturase 1 (SCD1) increased significantly. Bacteroides, Bifidobacteria, and Lactobacillus counts in feces decreased considerably, while Enterobacter cloacae increased. The activity of isocitrate lyase in feces increased markedly. Treatment of mice with saturated hydrogen led to decreased total cholesterol, total glyceride, and low-density lipoprotein and increased high-density lipoprotein in the peripheral blood. FAS and I-FAPB gene expression in the small intestine decreased. Bacteroides, Bifidobacteria, and Lactobacillus in feces increased significantly, whereas Enterobacter cloacae decreased. The activity of isocitrate lyase also diminished remarkably. These results suggest that saturated hydrogen could improve intestinal structural integrity and lipid metabolism disorders by inhibiting the glyoxylic acid cycle of the intestinal flora. Impact statement Past studies have shown that hydrogen can improve metabolic disorders, but its mechanism of action remains unclear. It is well known that metabolic diseases, such as obesity, are significantly associated with changes in the intestinal flora. The glyoxylic acid cycle is an essential metabolic pathway in prokaryotes, lower eukaryotes, and plants and could be the portal for mechanisms related to metabolic disorders. Many opportunistic pathogenic bacteria can recycle fatty acids to synthesize sugars and other pathogenic substances using the glyoxylic acid cycle. So, the glyoxylic acid cycle may be involved in intestinal dysbacteriosis under high-fat diet. This study, therefore, seeks to provide the mechanism of how hydrogen improves metabolic diseases and a new basis for the use of hydrogen in the treatment of metabolic disorders.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tieqiao Wang ◽  
Qiaomin Wu ◽  
Tingqi Zhao

Kaempferol is a dietary flavanol that regulates cellular lipid and glucose metabolism. Its mechanism of action in preventing hepatic steatosis and obesity-related disorders has yet to be clarified. The purpose of this research was to examine kaempferol’s antiobesity effects in high-fat diet- (HFD-) fed mice and to investigate its impact on their gut microbiota. Using a completely randomized design, 30 mice were equally assigned to a control group, receiving a low-fat diet, an HFD group, receiving a high-fat diet, and an HFD+kaempferol group, receiving a high-fat diet and kaempferol doses of 200 mg/kg in the diet. After eight weeks, the HFD mice displayed substantial body and liver weight gain and high blood glucose and serum cholesterol levels. However, treatment with kaempferol moderated body and liver weight gain and elevation of blood glucose and serum cholesterol and triglyceride levels. Examination of 16S ribosomal RNA showed that HFD mice exhibited decreased microbial diversity, but kaempferol treatment maintained it to nearly the same levels as those in the control group. In conclusion, kaempferol can protect against obesity and insulin resistance in mice on a high-fat diet, partly through regulating their gut microbiota and moderating the decrease in insulin resistance.


2019 ◽  
Vol 121 (10) ◽  
pp. 1097-1107 ◽  
Author(s):  
Serena Boscaini ◽  
Raul Cabrera-Rubio ◽  
John R. Speakman ◽  
Paul D. Cotter ◽  
John F. Cryan ◽  
...  

AbstractRecently there has been a considerable rise in the frequency of metabolic diseases, such as obesity, due to changes in lifestyle and resultant imbalances between energy intake and expenditure. Whey proteins are considered as potentially important components of a dietary solution to the obesity problem. However, the roles of individual whey proteins in energy balance remain poorly understood. This study investigated the effects of a high-fat diet (HFD) containing α-lactalbumin (LAB), a specific whey protein, or the non-whey protein casein (CAS), on energy balance, nutrient transporters expression and enteric microbial populations. C57BL/6J mice (n 8) were given an HFD containing either 20 % CAS or LAB as protein sources or a low-fat diet containing CAS for 10 weeks. HFD-LAB-fed mice showed a significant increase in cumulative energy intake (P=0·043), without differences in body weight, energy expenditure, locomotor activity, RER or subcutaneous and epididymal white adipose tissue weight. HFD-LAB intake led to a decrease in the expression of glut2 in the ileum (P=0·05) and in the fatty acid transporter cd36 (P<0·001) in both ileum and jejunum. This suggests a reduction in absorption efficiency within the small intestine in the HFD-LAB group. DNA from faecal samples was used for 16S rRNA-based assessment of intestinal microbiota populations; the genera Lactobacillus, Parabacteroides and Bifidobacterium were present in significantly higher proportions in the HFD-LAB group. These data indicate a possible functional relationship between gut microbiota, intestinal nutrient transporters and energy balance, with no impact on weight gain.


2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Hoe-Yune Jung ◽  
Yosep Ji ◽  
Na-Ri Kim ◽  
Do-Young Kim ◽  
Kyong-Tai Kim ◽  
...  

This study investigated the antiobesity effect of an extract of the Fomitopsis pinicola Jeseng-containing formulation (FAVA), which is a combination of four natural components:Fomitopsis pinicola Jeseng;Acanthopanax senticosus;Viscum album coloratum; andAllium tuberosum. High-fat diet- (HFD-) fed male C57BL/6J mice were treated with FAVA (200 mg/kg/day) for 12 weeks to monitor the antiobesity effect and amelioration of nonalcoholic fatty liver diseases (NAFLD). Body and white adipose tissue (WAT) weights were reduced in FAVA-treated mice, and a histological examination showed an amelioration of fatty liver in FAVA-treated mice without decreasing food consumption. Additionally, FAVA reduced serum lipid profiles, leptin, and insulin levels compared with the HFD control group. The FAVA extract suppressed lipogenic mRNA expression levels from WAT concomitantly with the cholesterol biosynthesis level in the liver. These results demonstrate the inhibitory effects of FAVA on obesity and NAFLD in the diet-induced obese (DIO) mouse model. Therefore, FAVA may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ningjing Zhang ◽  
Junxian Tao ◽  
Lijun Gao ◽  
Yan Bi ◽  
Ping Li ◽  
...  

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.


2020 ◽  
Vol 11 ◽  
Author(s):  
Huantian Cui ◽  
Yuting Li ◽  
Yuming Wang ◽  
Lulu Jin ◽  
Lu Yang ◽  
...  

The dysbiosis in gut microbiota could affect host metabolism and contribute to the development of nonalcoholic fatty liver disease (NAFLD). Da-Chai-Hu decoction (DCH) has demonstrated protective effects on NAFLD, however, the exact mechanisms remain unclear. In this study, we established a NAFLD rat model using a high fat diet (HFD) and provided treatment with DCH. The changes in gut microbiota post DCH treatment were then investigated using 16S rRNA sequencing. Additionally, serum untargeted metabolomics were performed to examine the metabolic regulations of DCH on NAFLD. Our results showed that DCH treatment improved the dyslipidemia, insulin resistance (IR) and ameliorated pathological changes in NAFLD model rats. 16S rRNA sequencing and untargeted metabolomics showed significant dysfunction in gut microbiota community and serum metabolites in NAFLD model rats. DCH treatment restored the dysbiosis of gut microbiota and improved the dysfunction in serum metabolism. Correlation analysis indicated that the modulatory effects of DCH on the arachidonic acid (AA), glycine/serine/threonine, and glycerophospholipid metabolic pathways were related to alterations in the abundance of Romboutsia, Bacteroides, Lactobacillus, Akkermansia, Lachnoclostridium and Enterobacteriaceae in the gut microflora. In conclusion, our study revealed the ameliorative effects of DCH on NAFLD and indicated that DCH’s function on NAFLD may link to the improvement of the dysbiosis of gut microbiota and the modulation of the AA, glycerophospholipid, and glycine/serine/threonine metabolic pathways.


2021 ◽  
Vol 32 (4) ◽  
pp. 547-553
Author(s):  
Mahardian Rahmadi ◽  
Ahmad Dzulfikri Nurhan ◽  
Eka Dewi Pratiwi ◽  
Devita Ardina Prameswari ◽  
Sisca Melani Panggono ◽  
...  

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD) is exceptionally common around the world. The development of NAFLD is increasing rapidly in the world, along with changes in lifestyle. Excess lipid intake is one of the risk factors for NAFLD. The NAFLD model is induced by a high-fat diet contains SFA, MUFA, and ῳ-6 PUFA. This study aims to assess the effect of high-fat diet variation on liver histology in developing NAFLD models in mice. Methods Thirty-six male mice (Balb/c) were divided into six groups fed a high-fat diet containing beef tallow 60%, beef tallow 45%, vegetable ghee, animal ghee + corn oil, vegetable ghee + corn oil for 28 days and compared to a control group fed a chow diet. All of the mice were fed with a high-fat diet in the form of pellets ad libitum for 28 days. Bodyweight and food intake were measured every day. At the last day of treatment, animals were sacrificed and the Liver were taken for histological analysis. Results This study showed that NAFLD model development was achieved in all group mice fed a high-fat diet with different degrees of NAFLD. Beef tallow 60% had the worst liver histology. Conclusions Thus, based on this study, we found that high-fat diet variations influenced the development of NAFLD models in mice, particularly concerning liver histology.


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