title: Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival.
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.
authors.affiliation: Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Narbonne
authors.forename: Richard
authors.initials: R
authors.lastname: Roy
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005215:Fasting / Q000502:physiology; D007814:Larva / Q000378:metabolism / Q000502:physiology; D008018:Life Cycle Stages / Q000502:physiology*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050356:Lipid Metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D040521:Subcutaneous Tissue / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases; C510541:AAK-2 protein, C elegans; D055372:AMP-Activated Protein Kinases; C534632:ATGL-1 protein, C elegans; D008049:Lipase