PMID- 29925242 OWN - NLM STAT- MEDLINE DCOM- 20190826 LR - 20190826 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 17 IP - 8 DP - 2018 Aug 3 TI - Beneficial Metabolic Effects of 2',3',5'-Triacetyl-N(6)-(3-hydroxylaniline) adenosine in Multiple Biological Matrices and Intestinal Flora of Hyperlipidemic Hamsters. PG - 2870-2879 LID - 10.1021/acs.jproteome.8b00330 [doi] AB - Hyperlipidemia is one of the main causes of obesity, type 2 diabetes mellitus (T2DM), and atherosclerosis. The adenosine derivative, 2',3',5'-triacetyl-N(6)-(3-hydroxylaniline) adenosine (IMM-H007) is an effective lipid-lowering compound that has important implications for the development of lipid-lowering drugs. Metabolomic analysis based on (1)H NMR was used to monitor dynamic changes in diverse biological media including serum, liver, urine, and feces in response to high-fat diet (HFD) and IMM-H007 treatments. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography (GC) analyses were performed to quantify the bile acids and fatty acids in the liver and feces. Fecal microbiome profiling was performed using Illumina sequencing of the 16S rRNA ( 16S rRNA) gene. IMM-H007 improved the metabolism of carbohydrate, ketone bodies, fatty acids, amino acids, and bile acids in hyperlipidemic hamsters. The correlation between metabolite changes was explored in different biological media. Significant changes in gut microbiota were observed in the HFD and IMM-H007 treatment groups. In the HFD group at the phylum level, we found high levels of the Firmicutes genus and low levels of Bacteroidetes. In contrast, the administration of IMM-H007 reversed the levels of Firmicutes and Bacteroidetes. This reversal suggested that IMM-H007 may have the ability to regulate the composition of the gut flora. We also analyzed the correlation between the gut flora and the metabolites. Our results indicate that IMM-H007 treatment improves the hyperlipidemic metabolism and the structure of the gut microbiota in hyperlipidemic hamsters. FAU - Li, Tianqi AU - Li T AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Sun, Shanshan AU - Sun S AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Zhang, Jinyue AU - Zhang J AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Qu, Kai AU - Qu K AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Yang, Liu AU - Yang L AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Ma, Changlu AU - Ma C AD - Department of Food and Biological Engineering , Beijing Vocational College of Agriculture , Beijing 100012 , China. FAU - Jin, Xiangju AU - Jin X AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Zhu, Haibo AU - Zhu H AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. FAU - Wang, Yinghong AU - Wang Y AUID- ORCID: 0000-0002-1396-3207 AD - State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100050 , China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180629 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (triacetyl-3-hydroxyphenyladenosine) RN - K72T3FS567 (Adenosine) MH - Adenosine/*analogs & derivatives/pharmacology/therapeutic use MH - Animals MH - Cricetinae MH - Diet, High-Fat/adverse effects MH - Gastrointestinal Microbiome/*drug effects MH - Hyperlipidemias/*drug therapy MH - Magnetic Resonance Spectroscopy MH - Metabolomics/methods OTO - NOTNLM OT - 2',3',5'-triacetyl-N6-(3-hydroxylaniline) adenosine OT - correlation analysis OT - intestinal flora OT - metabolomics EDAT- 2018/06/22 06:00 MHDA- 2019/08/27 06:00 CRDT- 2018/06/22 06:00 PHST- 2018/06/22 06:00 [pubmed] PHST- 2019/08/27 06:00 [medline] PHST- 2018/06/22 06:00 [entrez] AID - 10.1021/acs.jproteome.8b00330 [doi] PST - ppublish SO - J Proteome Res. 2018 Aug 3;17(8):2870-2879. doi: 10.1021/acs.jproteome.8b00330. Epub 2018 Jun 29.