Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival

Nature. 2009 Jan 8;457(7226):210-4. doi: 10.1038/nature07536. Epub 2008 Dec 3.

Abstract

Many organisms can enter a dormant state or diapause to survive harsh environmental conditions for extended durations. When Caenorhabditis elegans larvae enter dauer they arrest feeding but remain active and motile, yet become stress-resistant, extremely long-lived and non-ageing. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism, yet the precise molecular and physiological processes that enable long-term survival in the absence of caloric intake remain largely unknown. We show here that C. elegans larvae that lack LKB1/AMPK (AMP-activated protein kinase) signalling enter dauer normally, but then rapidly consume their stored energy and prematurely expire following vital organ failure. We found that this signalling pathway acts in adipose-like tissues to downregulate triglyceride hydrolysis so that these lipid reserves are rationed to last the entire duration of the arrest. Indeed, the downregulation of adipose triglyceride lipase (ATGL-1) activity suppresses both the rapid depletion of stored lipids and reduced life span of AMPK mutant dauers, while AMPK directly phosphorylates ATGL-1. Finally, we show that the slow release of energy during dauer is critical for appropriate long-term osmoregulation, which fails as triglyceride resources become depleted. These mechanisms may be essential for survival through diapause, hibernation, or long-term fasting in diverse organisms and may also underlie AMPK-dependent life span extension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / deficiency
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Adaptation, Physiological / physiology*
  • Animals
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Fasting / physiology
  • Larva / metabolism
  • Larva / physiology
  • Life Cycle Stages / physiology*
  • Lipase / antagonists & inhibitors
  • Lipase / metabolism
  • Lipid Metabolism*
  • Longevity / genetics
  • Longevity / physiology
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Signal Transduction
  • Subcutaneous Tissue / metabolism
  • Survival Analysis
  • Time Factors
  • Triglycerides / metabolism
  • Water-Electrolyte Balance / genetics

Substances

  • Caenorhabditis elegans Proteins
  • Triglycerides
  • Protein-Serine-Threonine Kinases
  • AAK-2 protein, C elegans
  • AMP-Activated Protein Kinases
  • ATGL-1 protein, C elegans
  • Lipase