The hormone leptin is tied to brain's control of eating

Appetite circuitry changes are surprise to scientists


New studies in mice suggest that the hormone leptin can fundamentally change the brain's circuitry in areas that control appetite. Leptin acts during a critical period early in life, possibly influencing how much animals eat as adults. And later in life, responding to how much fat is on an animal's body, it can again alter brain circuitry that controls how much is eaten.

Researchers say the findings, to be published today in the journal Science, are a surprise and help explain why weight control is so hard for some people.

Scientists knew that leptin is released by fat cells and that it tells the brain how much fat is on the body. They knew that animals lacking leptin become incredibly obese and that a few humans who, because of genetic mutations, do not make the hormone also are immensely fat.

Leptin injections immediately made animals, and the handful of patients with leptin deficiencies, lose their appetites. Their weight returned to normal.

But it was thought that leptin acted like most other hormones, attaching itself to brain cells and directly altering their activities.

Investigators did not expect that leptin could actually change connections in the brain, strengthening circuits that inhibit eating and weakening ones that spur appetite. And few considered the possibility that there might be a critical period early in life when the hormone shaped the brain's circuitry, possibly affecting appetite and obesity in adulthood.

"Obviously, we don't know what this looks like in humans," said Dr. Rudolph Leibel of Columbia University. "But it is possible that some of the differences in regulation of body weight that have been attributed to psychological processes or fat cell effects may be reflecting these ... processes."

In the first of two papers in Science, Dr. Richard B. Simerly and Dr. Sebastian G. Bouret at the Oregon Primate Research Center examined leptin's effects on the brain early in life. They gave leptin-deficient mice a surge of leptin early in life, mimicking what normal mice experience. It worked, reshaping the brain, and raised questions about what happens during normal development of mice, and people, that might determine whether they were destined to be fat or thin.

In the second paper, by Dr. Jeffrey M. Friedman, a Howard Hughes medical investigator at Rockefeller University, researchers examined two brain pathways that control appetite in adult mice. By examining the actual nerves in slices of brain, they saw that mice that make no leptin have strong brain circuits that signal them to eat, and weak circuits that signal them to stop eating.

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