A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans

Cell Metab. 2008 Sep;8(3):266-74. doi: 10.1016/j.cmet.2008.08.007.


Although studies in C. elegans have identified numerous genes involved in fat storage, the next step is to determine how these factors actually affect in vivo lipid metabolism. We have developed a (13)C isotope assay to quantify the contribution of dietary fat absorption and de novo synthesis to fat storage and membrane lipid production in C. elegans, establishing the means by which worms obtain and process fatty acids. We applied this method to characterize how insulin signaling affects lipid physiology. Several long-lived mutations in the insulin receptor gene daf-2 resulted in significantly higher levels of synthesized fats in triglycerides and phospholipids. This elevation of fat synthesis was completely dependent upon daf-16/FoxO. Other long-lived alleles of daf-2 did not increase fat synthesis, however, suggesting that site-specific mutations in the insulin receptor can differentially influence longevity and metabolism, and that elevated lipid synthesis is not required for the longevity of daf-2 mutants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Carbon Isotopes
  • Fatty Acids / biosynthesis
  • Fatty Acids / metabolism
  • Forkhead Transcription Factors
  • Insulin / metabolism*
  • Isotope Labeling
  • Lipids / physiology
  • Lipogenesis / physiology*
  • Membrane Lipids / biosynthesis
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • Carbon Isotopes
  • Fatty Acids
  • Forkhead Transcription Factors
  • Insulin
  • Lipids
  • Membrane Lipids
  • Transcription Factors
  • daf-16 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin