Mesocricetus auratus Raw sequence reads

Hyperlipidemia is a metabolic disorder related to the intestinal flora. To understand the mechanisms underlying hamster hyperlipidemia, we used NMR-based metabolomics and 16S rRNA gene sequencing to explore the changes of metabolites and intestinal flora and their relationship. We also examined energy redistribution during the hyperlipidemic state with metabolic flux technology ([U-13C6]glucose as isotope tracer). We observed enhanced fatty-acid ß-oxidation, suppressed tricarboxylic acid (TCA) cycle and amino acid metabolism, as well as significant disruption of gut microbiome-derived metabolites. Microbiome analysis revealed profound changes in gut microbial structure. As a result, dietary monosaccharide, protein, and fat fermentation were disrupted, affecting the energy pool for gut microbe activity. Metabolic flux confirmed impediments to glucose catabolism pathways. Specifically, TCA cycle activity decreased by 14.92%, pentose phosphate pathway (PPP) flux by 22.97%, and flux from conversion of [U-13C6]glucose to acylglycerol backbone by 34.51%. These results indicated a decrease in aerobic glucose oxidation, along with reduced ribose and NADPH production from the PPP, thus negatively influencing fatty acid synthesis and antioxidant stress. In conclusion, our results stem from three complementary analytical methods that verify each other, broadening our understanding of hyperlipidemia pathogenesis in a model rodent. Our findings should serve as an important reference for research strategies that can be used in future studies.