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]
