scholarly journals Serum and Liver Tissue Metabonomic Study on Fatty Liver in Rats Induced by High-Fat Diet and Intervention Effects of Traditional Chinese Medicine Qushi Huayu Decoction

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-jun Gou ◽  
Qin Feng ◽  
Lin-lin Fan ◽  
Jian Zhu ◽  
Yi-yang Hu

Qushi Huayu Decoction (QSHY), clinically derived, consists of five crude drugs, commonly used in treating fatty liver in a clinical setting. However, little is known about its metabolomics study. Herein, the serum and liver tissue metabolomics approach, based on gas chromatography coupled to spectrometry (GC/MS), was employed to evaluate the efficacy and the mechanism underlying QSHY in a rat model of high-fat diet-induced fatty liver. With pattern recognition analysis of serum and liver tissue metabolite profile, a clear separation of model group and control group was acquired for serum and liver tissue samples, respectively. The QSHY group showed a predisposition towards recovery mimicking the control group, which was in agreement with the biochemical alterations and histological results. 23 candidate biomarkers were identified in the serum and liver tissue samples that were utilized for exploring the underlying mechanism. The present study suggests that QSHY has significant anti-fatty liver effects on high-fat diet-induced fatty liver in rats, which might be attributed to regulating the dysfunction of beta-alanine metabolism, alanine, aspartate, and glutamate metabolism, glycine, serine, and threonine metabolism, pyruvate metabolism, and citrate cycle. Thus, metabolomics is a useful tool in the evaluation of the efficacy and elucidation of the mechanism underlying the complex traditional Chinese medicine prescriptions.

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiao-jun Gou ◽  
Shanshan Gao ◽  
Liang Chen ◽  
Qin Feng ◽  
Yi-yang Hu

Qushi Huayu Decoction (QHD), an important clinically proved herbal formula, has been reported to be effective in treating fatty liver induced by high-fat diet in rats. However, the mechanism of action has not been clarified at the metabolic level. In this study, a urinary metabolomic method based on gas chromatography-mass spectrometry (GC-MS) coupled with pattern recognition analysis was performed in three groups (control, model, and QHD group), to explore the effect of QHD on fatty liver and its mechanism of action. There was obvious separation between the model group and control group, and the QHD group showed a tendency of recovering to the control group in metabolic profiles. Twelve candidate biomarkers were identified and used to explore the possible mechanism. Then, a pathway analysis was performed using MetaboAnalyst 3.0 to illustrate the pathways of therapeutic action of QHD. QHD reversed the urinary metabolite abnormalities (tryptophan, uridine, and phenylalanine, etc.). Fatty liver might be prevented by QHD through regulating the dysfunctions of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and tryptophan metabolism. This work demonstrated that metabolomics might be helpful for understanding the mechanism of action of traditional Chinese medicine for future clinical evaluation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takuya Kawamura ◽  
Hiroaki Tanaka ◽  
Ryota Tachibana ◽  
Kento Yoshikawa ◽  
Shintaro Maki ◽  
...  

AbstractWe aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.


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.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Alexandra Becraft ◽  
Marlena Sturm ◽  
Gavin Pierce ◽  
Rufa Mendez ◽  
Neil Shay

Abstract Objectives Watermelon is a nutrient-dense fruit shown previously to produce health benefits, particularly regarding blood pressure regulation. We tested the hypothesis that intake of whole watermelon flesh and value-added watermelon components would improve metabolic conditions in C57BL/6 J male mice fed a high-fat, high-sucrose diet modeling an obesogenic Western diet (HF). We further hypothesize that metabolomic profiling will show changes in relative levels of compounds related to lipid and glucose metabolism, and chronic inflammation. Methods In a prior study (Becraft et al., 2018), groups of mice (n = 8) were provided either low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 45% kcal fat), HF plus Watermelon Skin (HF + WS), HF plus Watermelon Rind (HF + WR), or HF plus Watermelon Flesh (HF + WF) for 10 weeks. Watermelon flesh was provided at 10% of total energy and skin and rind were added at ∼ 0.2% (w/w) of diet. After ten weeks, animals were euthanized, and liver tissue saved for metabolomic analysis. Liver tissue samples were homogenized, and an identical mass equivalent of liver was subjected to methanol extraction and split into aliquots for analysis by ultrahigh performance liquid chromatography/mass spectrometry in the positive, negative or polar ion mode. There were 709 biochemicals identified and analyzed between groups. Welch's 2-sample t-test was performed with ArrayStudio (Omicsoft) or R software on log transformed data to compare data between experimental groups. Estimate of the false discovery rate (Q value) was calculated and Q ;< 0.05 used as an indication of high confidence in a result. Results Principal component analysis showed segregation of groups along three different components, representing 24.8%, 19.4%, and 9.0% of the variation. Profound differences were found in LF vs. HF liver tissue. Compared to HF-fed mice, mice fed WF showed reduced levels of bile acids and pro-inflammatory compounds 12-HETE, 15, HETE, and PGF2 (all P < 0.05) in the liver. Conclusions In mice consuming a high-fat western style diet, regular intake of watermelon flesh, and fiber-rich products made from rind and skin all improved metabolism as evidenced by metabolomic analysis of liver tissue. Most notably were reductions in pro-inflammatory compounds including HETEs and Prostaglandin F2. Funding Sources National Watermelon Promotion Board.


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.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tian-hong Xie ◽  
Jun-xiang Li ◽  
Tang-you Mao ◽  
Yi Guo ◽  
Chen Chen ◽  
...  

ErChen and YinChen decoction (ECYCD) is an effective traditional Chinese medicine and has been widely used in traditional Chinese medicine to treat nonalcoholic steatohepatitis (NASH), with good curative effects. However, the specific mechanisms underlying these effects are unclear. In this study, we determined the efficacy of ECYCD in a high-fat diet-induced NASH rat model, established by 8-week administration of a high-fat diet. ECYCD was administered daily for 4 weeks, after which the rats were euthanized. The results demonstrated that ECYCD ameliorated high-fat diet-induced NASH, as evidenced by decreased liver indexes, reduced hepatic lipid deposition and liver injury, lower serum biochemistry markers (including low-density lipoprotein), and reduced HOMA-IR scores. Moreover, levels of free fatty acids, tumor necrosis factor, and malondialdehyde were decreased, whereas glutathione was increased in the liver. Serum high-density lipoprotein was also increased in the liver, and ECYCD regulated the c-Jun N-terminal kinase 1 (JNK1) signaling pathway by decreasing the levels of JNK1 protein,JNK1mRNA, activator protein- (AP-) 1 protein,AP-1mRNA, and phospho-insulin receptor substrate- (IRS-)1ser307and increasing phopsho-PKBser473levels. These results suggested that ECYCD could ameliorate high-fat diet-induced NASH in rats through JNK1 signaling. ECYCD may be a safe therapeutic option for the treatment of NASH.


Epigenomics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1267-1282 ◽  
Author(s):  
Zupeng Luo ◽  
Zhiwang Zhang ◽  
Lina Tai ◽  
Lifang Zhang ◽  
Zheng Sun ◽  
...  

Aim: To assess the m6A methylome in mouse fatty liver induced by a high-fat diet (HFD). Materials & methods: MeRIP-seq was performed to identify differences in the m6A methylomes between the normal liver and fatty liver induced by an HFD. Results: As compared with the control group, the upmethylated coding genes upon feeding an HFD were primarily enriched in processes associated with lipid metabolism, while genes with downmethylation were enriched in processes associated with metabolism and translation. Furthermore, many RNA-binding proteins that potentially bind to differentially methylated m6A sites were mainly annotated in processes of RNA splicing. Conclusion: These findings suggest that differential m6A methylation may act on functional genes through RNA-binding proteins to regulate the metabolism of lipids in fatty liver disease.


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