Disparate Metabolomic Responses to Fructose Consumption between Different Mouse Strains and the Role of Gut Microbiota.
In Sook AhnJustin YoonGraciel DiamantePeter CohnCholsoon JangXia YangPublished in: Metabolites (2021)
High fructose consumption has been linked to metabolic syndrome, yet the fructose-induced phenotypes, gene expression, and gut microbiota alterations are distinct between mouse strains. In this study, we aim to investigate how fructose consumption shapes the metabolomic profiles of mice with different genetic background and microbiome. We used fructose-sensitive DBA/2J (DBA) and fructose-resistant C57BL/6J (B6) mice given 8% fructose or regular water for 12 weeks. Plasma and fecal metabolites were profiled using a liquid chromatography-tandem mass spectrometry based global metabolomic approach. We found that the baseline metabolomic profiles were different between DBA and B6 mice, particularly plasma metabolites involved in lipid metabolism and fecal metabolites related to dipeptide/amino acid metabolism. In response to fructose, DBA mice showed a distinct decrease of plasma branched chain fatty acids with concordantly increased branched chain amino acids, which were correlated with adiposity; B6 mice had significantly increased plasma cholesterol and total bile acids, accompanied by decreased fecal levels of farnesoid X receptor antagonist tauro-β-muricholate, which were correlated with fructose-responsive bacteria Dehalobacterium, Magibacteriaceae, and/or Akkermansia. Our results demonstrate that baseline metabolomic profiles differ and respond differentially to fructose between mice with different genetic background and gut microbiota, which may play a role in individualized risks to fructose-induced metabolic syndrome.
Keyphrases
- metabolic syndrome
- high fat diet induced
- gene expression
- amino acid
- liquid chromatography tandem mass spectrometry
- ms ms
- insulin resistance
- fatty acid
- type diabetes
- dna methylation
- oxidative stress
- wild type
- risk assessment
- diabetic rats
- solid phase extraction
- high glucose
- cancer therapy
- endothelial cells
- uric acid
- stress induced
- gestational age