Beneficial Metabolic Effects of 2 ',3 ',5 '-Triacetyl-N-6-(3-hydroxylaniline) adenosine in Multiple Biological Matrices and Intestinal Flora of Hyperlipidemic Hamsters

摘要

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 H-1 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.