Systemic regulation of starvation response in Caenorhabditis elegans.

When the supply of environmental nutrients is limited, multicellular animals can make both physiological and behavioral changes so as to cope with nutrient starvation. Although physiological and behavioral effects of starvation are well known, the mechanisms by which animals sense starvation systemically remain elusive. Furthermore, what constituent of food is sensed and how it modulates starvation response is still poorly understood. In this study, we use a starvation-hypersensitive mutant to identify molecules and mechanisms that modulate starvation signaling. We found that specific amino acids could suppress the starvation-induced death of gpb-2 mutants, and that MGL-1 and MGL-2, Caenorhabditis elegans homologs of metabotropic glutamate receptors, were involved. MGL-1 and MGL-2 acted in AIY and AIB neurons, respectively. Treatment with leucine suppressed starvation-induced stress resistance and life span extension in wild-type worms, and mutation of mgl-1 and mgl-2 abolished these effects of leucine. Taken together, our results suggest that metabotropic glutamate receptor homologs in AIY and AIB neuron may modulate a systemic starvation response, and that C. elegans senses specific amino acids as an anti-hunger signal.