Satisfied Worms

Abstract

The rise in the incidence of obesity has stimulated interest in determining the mechanisms that are involved in controlling appetite and thus preventing overeating. Discovering the signals responsible for making a person feel satisfied (or satiated) after eating might help in the development of therapies to prevent obesity. You et al . used the worm Caenorhabditis elegans as a model system to study the factors that control appetite. C . elegans normally feed and move constantly when food is available, but the authors found that worms exposed to a high-quality (high nutritional value) food source gradually decreased their rates of food intake and movement, compared with those of worms exposed to low-quality food. The former worms entered a state of quiescence that resembled the resting state of satiated mice. Mutant C. elegans that had a defect in nutrient absorption from the intestine were less quiescent than their wild-type counterparts. Mutant C. elegans that were singly deficient in the worm homologs of insulin, transforming growth factor-β (TGF-β), or either of the receptors for TGF-β exhibited much shorter periods of quiescence compared with those of wild-type worms. C . elegans with a loss-of-function mutation in the cGMP-dependent protein kinase (PKG) homolog EGL-4 (which is downstream of insulin and TGF-β) are known to be larger and more migratory than wild-type C . elegans . The authors found that egl-4 loss-of-function mutants never entered a state of quiescence during feeding, whereas egl-4 gain-of-function mutants showed a longer duration of quiescence than did wild-type worms. Finally, worms deficient in the enzyme that synthesizes cGMP had a shorter duration of quiescence than did wild-type worms. This study suggests that insulin- and TGF-β-mediated signals through PKG may serve as targets of therapies against obesity. Y.-j. You, J. Kim, D. M. Raizen, L. Avery, Insulin, cGMP, and TGF-β signals regulate food intake and quiescence in C . elegans : A model for satiety. Cell Metab . 7 , 249-257 (2008). [PubMed]