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-ageing1. Entry into dauer is associated with a reduction in insulin-like signalling, the accumulation of nutritive resources and a concomitant global change in metabolism2,3,4,5, 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.

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Figure 1: aak-2 functions in the hypodermis and excretory system to regulate dauer survival.
Figure 2: aak-2 blocks ATGL-1-mediated triglyceride hydrolysis to ensure long-term dauer survival.
Figure 3: aak-2 is required for proper osmoregulation during dauer.

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Acknowledgements

We thank A. Fire, O. Hobert, I. Greenwald, D. Baillie, K. Nehrke, J. McGhee, M. Han, S. Li, E. Colella, M. Hebeisen, J. Ouellet, A. Shingina, M. Maduro, F. Solari, E. Greer, J. Lapointe, W. Yang and S. Hekimi for reagents, strains, constructs, help, advice and support. Some of the strains that were used in this analysis came from the Caenorhabditis Genetic Center (CGC), the C. elegans Gene Knockout Consortium, the Japan National Bioresource Project, and the Genome BC C. elegans Gene Expression Consortium. This work was supported by research grants from the Canadian Cancer Society and the Canadian Institutes of Health Research (CIHR) to R.R. P.N. is a recipient of an NSERC studentship. R.R. is a CIHR New Investigator.

Author Contributions P.N. designed and conducted all the experiments, except the kinase assays, which were performed by R.R.. The manuscript was written by P.N. and edited by R.R.

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Correspondence to Richard Roy.

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Narbonne, P., Roy, R. Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. Nature 457, 210–214 (2009). https://doi.org/10.1038/nature07536

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