<p>Obesogenic diets induce systemic and gut luminal metabolic perturbations, but whether these alterations occur in parallel across biospecimens remains unclear. In particular, the extent to which high-fat diet (HFD) and Western diet (WD) produce shared or compartment-specific metabolic responses in circulation and feces has not been systematically compared. In this study, targeted LC-MS/MS-based metabolite profiling was performed using serum and fecal samples from mice fed a normal diet (ND), HFD, or WD. Serum samples were analyzed at the individual-animal level, whereas fecal samples were analyzed as cage-level pooled specimens and interpreted as exploratory. Group differences were assessed using non-parametric statistics with Benjamini-Hochberg false discovery rate correction, followed by cross-compartment comparison of HFD-versus-ND and WD-versus-ND directional changes among metabolites detected in both matrices. In serum, obesogenic diets were associated with significant alterations in branched-chain amino acid-related metabolites, phenylalanine, serotonin, butyrylcarnitine, and taurocholic acid. In exploratory fecal metabolomics, significant diet-associated differences were observed mainly in amino acid-related metabolites, cholic acid, and 3-indolepropionic acid. Cross-compartment comparison of HFD-versus-ND and WD-versus-ND responses showed that several amino acid-related metabolites, including valine, leucine, and phenylalanine, were decreased in serum but increased in feces. WD also showed fecal bile acid- and indole-related changes in the exploratory fecal dataset under the present conditions. These findings suggest that HFD and WD are associated with distinct and compartment-specific metabolic remodeling across circulating and luminal compartments and support the value of multi-compartment metabolomics in studies of diet-associated metabolic dysfunction.</p>

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Integrated serum and fecal metabolomics identifies compartment-specific metabolic remodeling in mice fed high-fat and Western diets

  • Yu Ra Lee,
  • Hye-Bin Lee,
  • Hee-Jin Kim,
  • Jae-Ho Park,
  • Ho-Young Park

摘要

Obesogenic diets induce systemic and gut luminal metabolic perturbations, but whether these alterations occur in parallel across biospecimens remains unclear. In particular, the extent to which high-fat diet (HFD) and Western diet (WD) produce shared or compartment-specific metabolic responses in circulation and feces has not been systematically compared. In this study, targeted LC-MS/MS-based metabolite profiling was performed using serum and fecal samples from mice fed a normal diet (ND), HFD, or WD. Serum samples were analyzed at the individual-animal level, whereas fecal samples were analyzed as cage-level pooled specimens and interpreted as exploratory. Group differences were assessed using non-parametric statistics with Benjamini-Hochberg false discovery rate correction, followed by cross-compartment comparison of HFD-versus-ND and WD-versus-ND directional changes among metabolites detected in both matrices. In serum, obesogenic diets were associated with significant alterations in branched-chain amino acid-related metabolites, phenylalanine, serotonin, butyrylcarnitine, and taurocholic acid. In exploratory fecal metabolomics, significant diet-associated differences were observed mainly in amino acid-related metabolites, cholic acid, and 3-indolepropionic acid. Cross-compartment comparison of HFD-versus-ND and WD-versus-ND responses showed that several amino acid-related metabolites, including valine, leucine, and phenylalanine, were decreased in serum but increased in feces. WD also showed fecal bile acid- and indole-related changes in the exploratory fecal dataset under the present conditions. These findings suggest that HFD and WD are associated with distinct and compartment-specific metabolic remodeling across circulating and luminal compartments and support the value of multi-compartment metabolomics in studies of diet-associated metabolic dysfunction.