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Metabotyping of Caenorhabditis elegans and their Culture Media Revealed Unique Metabolic Phenotypes Associated to Amino Acid Deficiency and Insulin-Like Signaling

2011; American Chemical Society; Volume: 10; Issue: 3 Linguagem: Inglês

10.1021/pr100703a

1535-3907

François‐Pierre Martin, Britta Spanier, Sebastiano Collino, Ivan Montoliu, Carolin A. Kolmeder, Pieter Giesbertz, Michael Affolter, Martin Kussmann, Hannelore Daniel, Sunil Kochhar, Serge Rezzi,

Gut microbiota and health

Insulin/IGF-like signaling (IIS) and nutrient sensing are among the most potent regulators of health status and aging. Here, a global view of the metabolic changes in C. elegans with impaired function of IIS represented by daf-2 and daf-16 and the intestinal di- and tripeptide transport pept-1 was generated using (1)H nuclear magnetic resonance spectroscopic analysis of worm extracts and spent culture media. We showed that specific metabolic profiles were significantly associated with each type of mutant. On the basis of the metabonomics data, selected underlying processes were further investigated using proteomic and transcriptomic approaches. The observed changes suggest a decreased activity of the one carbon metabolism in pept-1(lg601) mutants. Higher concentration of branched-chain amino acids (BCAA) and altered transcript levels of genes involved in BCAA metabolism were observed in long-living strains daf-2(e1370) and daf-2(e1370);pept-1(lg601) when compared to wild types and daf-16(m26);daf-2(e1370);pept-1(lg601) C. elegans, suggesting a DAF-16-dependent mechanism.