ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C. elegans

Mol Metab. 2019 Sep:27:75-82. doi: 10.1016/j.molmet.2019.07.001. Epub 2019 Jul 5.


Objective: Animal lifespan is controlled through genetic pathways that are conserved from nematodes to humans. Lifespan-promoting conditions in nematodes include fasting and a reduction of insulin/IGF signaling. Here we aimed to investigate the input of the Caenorhabditis elegans homologue of the mammalian rate-limiting lipolytic enzyme Adipose Triglyceride Lipase, ATGL-1, in longevity control.

Methods: We used a combination of genetic and biochemical approaches to determine the role of ATGL-1 in accumulation of triglycerides and regulation of longevity.

Results: We found that expression of ATGL is increased in the insulin receptor homologue mutant daf-2 in a FoxO/DAF-16-dependent manner. ATGL-1 is also up-regulated by fasting and in the eat-2 loss-of-function mutant strain. Overexpression of ATGL-1 increases basal and maximal oxygen consumption rate and extends lifespan in C. elegans. Reduction of ATGL-1 function suppresses longevity of the long-lived mutants eat-2 and daf-2.

Conclusion: Our results demonstrate that ATGL is required for extended lifespan downstream of both dietary restriction and reduced insulin/IGF signaling.

Keywords: ATGL-1; C. elegans; DAF-16; DAF-2; Dietary restriction; Longevity.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Fasting
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Lipase / metabolism*
  • Longevity
  • Signal Transduction*


  • Caenorhabditis elegans Proteins
  • Insulin
  • Insulin-Like Growth Factor I
  • ATGL-1 protein, C elegans
  • Lipase