Mammalian target of rapamycin (mTOR) is well known to cancer researchers, as well as biotech firms, as a protein kinase involved in the control of cell growth.

In the May 12, 2006, issue of Science, researchers from the University of Cincinnati showed that mTOR serves to control growth at the organism level, as well. In the brain's feeding control center, mTOR expression can be induced by both the amino acid leucine and the hormone leptin, and that activation leads to reduced food intake by animals.

Hormones have received much of the recent attention in appetite control research, basic and pharmaceutical. While hormones signal how much fuel is available stored as fat, leucine signals the availability of fuel from the most recent meal. The Science paper showed that the two signals are integrated in the hypothalamic area known as the arcuate nucleus.

The researchers found that in the brain, though, mTOR and its downstream target S6 kinase 1 are expressed pretty much everywhere, their phosphorylated and thus active forms are found mainly in two hypothalamic nuclei that are involved in feeding. Whether animals had recently eaten or not affected phosphorylation status of mTOR and S6 kinase 1 in the arcuate nucleus, but not elsewhere.

In animal studies, leucine (but not a related amino acid) decreased the food intake when given directly into the brain. Inhibiting mTOR signaling prevented leucine from having an effect on feeding. Inhibiting mTOR activation also prevented the appetite-suppressing effects of leptin, which regulates food intake by signaling the state of fat stores.

Senior author Randy Seeley, associate professor of psychiatry at the University of Cincinnati, compared the integration of hormone and fuel signals to counting up money: "To make spending decisions, you need to know how much money is in your checking account and how much cash you have in your pocket," he told BioWorld Today.

Alas, if only it were as easy to spend calories as money. Americans are fat and getting fatter. In fact, a few weeks ago, they got massively fatter with the stroke of a pen - research published in the May 2006 issue of the Journal of the Royal Society of Medicine showed that current estimates of obesity rates, which are based on telephone surveys, need to be corrected upward by 50 percent - women tended to report too few pounds and men too many inches, both of which led to an underestimation of their body mass index.

Even aside from rooting out measuring error, obesity rates have been growing steadily for the last 30 years. The reasons behind the increase are not entirely clear, though some contributing factors are fairly obvious: Food is relatively cheaper than it has ever been and more abundant.

More subtly, changes in sweeteners have probably led to foods that are not as readily metabolized. On the output side, there also is less need to metabolize food for energy: Between remote controls and drive-throughs, it appears that the day approaches when there will be no need to move whatsoever.

As for exploiting the findings to make a dent in the obesity epidemic, though an accompanying commentary suggested that "the next challenge will be to determine whether novel therapies for metabolic disease will emerge from pharmacological or nutritional exploitation of these insights," Seeley himself was somewhat skeptical of this approach, at least in its most simple incarnation of trying to inhibit mTOR or its downstream targets.

He said that though mTOR has shown some promise as a cancer therapy target, cancer cells "are growing very fast and so depend a great deal on high mTOR activity to engage in protein synthesis and grow." In contrast, "for obesity, you would be trying to knock down 'normal' mTOR activity and in doing so would inhibit in lots of cells in the brain and other places. The many processes linked to mTOR would be potentially disrupted and increase the probability of unwanted side effects," since mTOR is very widely expressed.

Indeed, leptin already has fizzled in the clinic, though for a different reason; while it can be used to treat people who cannot make the hormone themselves, most obese people make plenty of leptin but are insensitive to its appetite-suppressant effects.

Looks like it may be time to dust off those running shoes after all. Or lie about your height or weight.