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

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

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1
Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada.

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.

PMID:
19052547
DOI:
10.1038/nature07536
[Indexed for MEDLINE]
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