Apr 7 2006
New evidence in Cell Metabolism reveals a molecular mechanism that may play a general role in animals' ability to respond appropriately when starved. The researchers discovered a pathway in worms that underlies their ability to adapt to food scarcity by remodeling their primary feeding organ.
In combination with earlier evidence, the findings suggest the so-called muscarinic acetylcholine pathway might play a conserved role in animals' starvation response, the researchers said. The new findings might ultimately yield insights into the connection between eating disorders and an abnormal response to hunger or starvation, they suggest.
"In the nematode worm C. elegans, starvation causes a variety of changes in development, longevity, and behavior," said Young-jai You of the University of Texas Southwestern Medical Center. One such behavioral change involves alterations to the animals' main feeding organ, the pharynx.
The worms eat by "pumping" bacteria in via relaxation and contraction of their pharyngeal muscle--an activity controlled by their internal feeding status. However, the signal responsible for changes in pumping rate had yet to be found.
The research team now reports that starvation activates the enzyme MAPK in the pharyngeal muscles of C. elegans through a muscarinic acetylcholine receptor. Mutations and drugs that prevented any step of the signal from muscarinic receptor to MAPK blocked the effects of starvation on the feeding muscle, they found. Furthermore, an excess of MAPK in normal worms mimicked the effect of starvation on the muscle.
"In mammals, muscarinic acetylcholine receptors regulate heart muscle and smooth muscle of the [digestive] tract, and MAPK signaling activation downstream of muscarinic acetylcholine receptors has been widely noted," wrote Kaveh Ashrafi in a Preview. "Moreover, there are intriguing but conflicting reports on the role of the receptors in growth rate and body weight of rodents.
"It is therefore plausible that molecular mechanisms that mediate starvation responses of C. elegans pharyngeal muscle are conserved across phylogeny," Ashrafi said.
The findings might help to unravel the factors underlying eating disorders, the researchers said.
"Despite the prevalence of feeding disorders from obesity to anorexia, the identity and mechanism of action of starvation signals are largely unknown," You's team added. "Our study of starvation sensitivity of gpb-2 mutants and the downstream signaling pathway in feeding muscles suggests that feeding disorders may result from inappropriate behavioral responses to starvation signals."
http://www.cellmetabolism.org
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