Jolly No More

New research is piecing together the answers to fat�s ponderous puzzle.

BARRY SHERMAN, M.D.

Science has taken all the fun out of being fat. Once a sign of power, or at least of possessing good humor, chubbiness is now blamed for a familiar litany of woes intoned in every magazine, chat show, and surgeon general�s speech. Heart attacks, diabetes, depression, and death�the extra pounds will bring them all on. Despite the bad news, people are piling it on as never before. Sixty percent of U.S. adults are said to be overweight, and children have become obese even more quickly than their parents. Telling people that being overweight is bad for them seems to have little effect, so science now is trying to come up with something stronger than admonitions and earnestness.

The search for a technological fix starts with the distant past, when survival meant making the most of scant food.

Until only recently, scraping together even a subsistence diet took substantial energy for most people. Evolution has bequeathed mankind highly efficient systems for extracting maximum energy from any available caloric source and for storing it efficiently for times when food might be in short supply. People are thrifty creatures who have developed metabolic systems beautifully designed to protect against starvation.

In the past year, investigators have pulled together 40 years� worth of disparate research to form a coherent picture of these metabolic pathways (see �A Healthy Appetite,� below).¹ The picture evokes familiar patterns. It turns out that appetite, like other metabolic functions such as gonadal and thyroid activity, is regulated by chemical signals between the brain and the rest of the body.

1  Batterham, R.L. et al. (September 4, 2003) Inhibition of food intake in obese subjects by peptide YY3-36. New England Journal of Medicine 349:926�8.