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Obesity may not be directly due to eating

June 3, 2008
Courtesy Cell Press
and World Science staff

Wheth­er you’re fat or thin is only in­di­rectly de­ter­mined by your eat­ing habits, sug­gest re­search­ers who re­port new find­ings with a study us­ing worms.

They found that both eat­ing and fat in worms de­pends on lev­els of a sub­stance called ser­o­to­nin in the nerv­ous sys­tem. Yet it seems the “con­trol of fat is dis­tinct from” that of eat­ing, said Ka­veh Ash­rafi of the Uni­ver­s­ity of Cal­i­for­nia, San Fran­cis­co, one of the sci­en­tists.
The re­search­ers found ev­i­dence that ser­o­to­nin, which acts as a mes­sen­ger be­tween nerve cells, works through in­de­pend­ent chan­nels to con­trol wheth­er you eat ver­sus what to do with those calo­ries once you’ve eat­en them.

“These out­puts are re­lat­ed, but they are not con­se­quenc­es of each oth­er. It’s not that feed­ing is­n’t im­por­tant,” Ash­rafi added. The find­ings ap­pear in the June is­sue of the re­search jour­nal Cell Me­tab­o­lism. 

Ash­rafi sus­pects at a fun­da­men­tal lev­el the worm find­ings can be ex­trap­o­lated to hu­mans, giv­en ser­o­to­nin’s an­cient ev­o­lu­tion­ary ori­gins. 

This in turn may mean one could de­vel­op ther­a­pies “to ma­ni­pu­late fat me­tab­o­lism in­de­pend­ently of what you eat,” he said. “Now, the fo­cus is pri­marily on feed­ing be­hav­ior. As im­por­tant as that is, it’s only part of the sto­ry… it may be one rea­son di­ets fail.”

While fat regula­t­ion is at one lev­el a rel­a­tively sim­ple bal­ance be­tween en­er­gy in­take and out­put, the phys­i­ol­o­gy is none­the­less quite com­plex, Ash­rafi said. The re­search­ers at­tempted to dis­sect that com­plex­ity us­ing the worm C. el­e­gans, which is much sim­pler to work with than mam­mals.

They found in the worms that ser­o­to­nin’s con­trol of eat­ing in­volves mo­le­cules not needed for fat con­trol. Its ef­fects on fat de­pend on a sep­a­rate neu­ral chan­nel and mo­le­cules that spark sig­nals lead­ing to the break­down of fat, Ash­rafi said; the byprod­ucts of that pro­cess then come “full cir­cle” and gov­ern feed­ing be­hav­ior.

The find­ings show that, as in mam­mals, C. el­e­gans eat­ing de­pends on both in­ter­nal and en­vi­ron­men­tal cues, the re­search­ers wrote: “feed­ing be­hav­ior and fat me­tab­o­lism are co­or­di­nated but in­de­pend­ent re­sponses of the nerv­ous sys­tem to the per­cep­tion of nu­tri­ent avail­abil­ity.”

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Whether you’re fat or thin is only indirectly determined by your eating habits, suggest researchers who report new findings with a study using worms. They found that both feeding and fat in worms depends on levels of a substance called serotonin in the nervous system. But it also found the “control of fat is distinct from” that of feeding, said Kaveh Ashrafi of the University of California, San Francisco, one of the scientists. The researchers found evidence that serotonin, which acts as a messenger between nerve cells, acts through independent channels to control whether you eat versus what to do with those calories once you’ve eaten them. “These outputs are related, but they are not consequences of each other. It’s not that feeding isn’t important,” Ashrafi added. The findings appear in the June issue of the research journal Cell Metabolism. Ashrafi suspects at a fundamental level the worm findings can be extrapolated to humans, given serotonin’s ancient evolutionary origins. This in turn may mean one could develop therapies “to manipulate fat metabolism independently of what you eat,” he said. “Now, the focus is primarily on feeding behavior. As important as that is, it’s only part of the story… it may be one reason diets fail.” While fat regulation is at one level a relatively simple balance between energy intake and output, the physiology is nonetheless quite complex, Ashrafi said. The researchers attempted to dissect that complexity using the worm C. elegans, which is much simpler to work with than mammals. They found in the worms that serotonin’s control of feeding involves molecules not needed for fat control. Serotonin’s effects on fat depend on a separate neural channel and molecules that spark signals leading to the breakdown of fat, Ashrafi said; the byproducts of that process then come “full circle” and govern feeding behavior. The findings show that, as in mammals, C. elegans feeding behavior depends on both internal and environmental cues, the researchers wrote: “feeding behavior and fat metabolism are coordinated but independent responses of the nervous system to the perception of nutrient availability.”