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Appetite-Killing Hormone Negates Joy of Eating

Leptin puts a double whammy on hunger by making food less rewarding
brain scan



COURTESY OF SADAF FAROOQI
Ever wonder how your body knows not to gorge itself to death on food? The hormone leptin brings about that well-known feeling of fullness, and now a study finds that after we've dined, leptin puts the brake on our taste for food, too.

Researchers scanned the brains of two voracious teenagers whose fat cells were unable to secrete leptin normally, but after being given the hormone for a week became pickier eaters. Leptin treatment reduced the activity in a brain region that perks up when we see ice cream and other foods we enjoy, according to a report in Science.

The result forges the first link in people between the regulation of hunger and fullness on one hand and the "liking" of food on the other, says obesity researcher and study co-leader Sadaf Farooqi, a Wellcome Trust clinical scientist at Addenbrooke's Hospital in Cambridge, England. Identifying the other molecules at work in these intertwined pathways as well as from ongoing studies of similar pathways may lead to new weight control drugs within the decade, she says.

The two leptin-deficient kids—a 14-year-old boy and 19-year-old girl—are among a dozen in the world with a congenital lack of leptin, which keeps them feeling perpetually starved despite being severely obese, Farooqi says.

Like the others who lack the hormone, the teens began taking replacement injections, so Farooqi, along with brain scanner Paul Fletcher and other Addenbrooke's colleagues, took advantage.

They placed each kid in a functional magnetic resonance imaging (fMRI) machine and asked them to rate how much they liked images ranging from bland foods such as cauliflower and plain noodles to mouthwatering sweets including cakes and ice cream. The telling ratings were those made after noshing.

Before starting leptin, they graded the images an average of 8.9 out of 10. "They really like all foods," Farooqi says. The individual scores matched up well with the degree of activity in a brain region called the nucleus accumbens, the researchers report.

But during the first week of leptin treatment, the kids got full faster and were less hungry and more selective about what they ate. In accord with their new choosey eating habits, their postfeeding image ratings fell to an average of 5.9, and nucleus accumbens activity was more erratic.

"Leptin allows them to discriminate between appetizing and bland foods," Farooqi says, in the same way that regular subjects did when they had already eaten.

Studies suggest that genetics accounts for 40 to 70 percent of adult body weight, but researchers don't know all the culprits. Four years ago, Farooqi's group discovered that a separate mutation in the gene for melanocortin-4 receptor shows up in 1 percent of obese people and 5 to 6 percent of severely obese children.

Studying the leptin pathway will likely reveal many other genes that influence eating habits, she says. For hungry obesity researchers, leptin is quite a meal.

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