Integrated omics analysis unraveled the microbiome-mediated effects of Yijin-Tang on hepatosteatosis and insulin resistance in obese mouse |
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| Institution: | 1. Clinical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea;2. Non-clinical Collaboration Team, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea;1. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China;2. College of Food and Bioengineering, South China University of Technology, Guangzhou 510640, China;1. Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea.;2. Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea.;3. Department of Food Science and Nutrition, Kyungpook National University, Daegu 41566, Republic or, Republic of Korea.;4. Department of Chemistry & Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.;1. Zhejiang Chinese Medical University, Hangzhou 310053, China;2. Zhejiang University of Technology, Hangzhou 310014, China;3. Department of Traditional Chinese Medicine, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China;4. Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China;1. Korea Medicine Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea;2. Pharmaceutical Analysis Team, International Scientific Standards, Chuncheon 24232, Republic of Korea;3. Internal Medicine, College of Korean Medicine, Semyung University, Jecheon 27136, Republic of Korea;4. Department of Pediatrics, College of Korean Medicine, Semyung University, Jecheon 27136, Republic of Korea |
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| Abstract: | BackgroundGut 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.PurposeOur aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile.MethodsC57BL/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.ResultsYJT 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.ConclusionThese 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. |
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