Editors' ChoiceMetabolism

Staving Off Hunger

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Science Signaling  20 Jan 2009:
Vol. 2, Issue 54, pp. ec19
DOI: 10.1126/scisignal.254ec19

Starvation induces systemic changes in multicellular organisms, and Kang and Avery report that several amino acids act as signals that modulate these responses in the nematode Caenorhabditis elegans. Animals homozygous for loss-of-function mutations in gpb-2, which encodes a G protein β subunit, are hypersensitive to starvation; most mutant animals fail to recover in the presence of food after 4 days of starvation and exhibit increased autophagy in the pharynx. Treating gpb-2 mutants with leucine, glutamine, alanine, valine, or isoleucine by briefly soaking them in an amino acid–containing buffer before starvation increased the number of animals that were able to recover after 4 days of starvation and decreased pharyngeal autophagy. Because metabotropic glutamate receptors (mGluRs) can sense amino acids, the authors tested whether mGluRs mediated this effect. Mutation of either mgl-1 or mgl-2, which encode mGluRs, partially suppressed starvation hypersensitivity and pharyngeal autophagy, and mutation of both had an additive effect. Amino acid treatment had an additive effect on recovery in gpb-2; mgl-1 and gpb-2; mgl-2 mutants, but gpb-2; mgl-1; mgl-2 triple mutants were refractory to amino acid treatment, indicating that the amino acid signal could be transduced by either receptor. Starvation experiments in wild-type worms illustrated that these five amino acids also signaled through MGL-1 and MGL-2 to repress starvation responses in normal animals. MGL-1 was required only in the AIY neuron, which is activated in the presence of food, and MGL-2 was required only in the AIB neuron, which is activated in the absence of food. The authors conclude that leucine, glutamine, alanine, valine, and isoleucine are antihunger signals that induce signaling through mGluRs in sensory neurons to modulate the systemic response to starvation.

C. Kang, L. Avery, Systemic regulation of starvation response in Caenorhabditis elegans. Genes Dev. 23, 12–17 (2009). [Abstract] [Full Text]

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