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Fat Hormone Can Rewire Brain, Animal Studies Show
Reuters Health
By Maggie Fox
Friday, April 2, 2004
WASHINGTON (Reuters) - Leptin, a hormone that affects weight and appetite, apparently helps wire the brain in ways that might set an animal on a lifetime path to slenderness or obesity, two teams of U.S. researchers said on Thursday.
The studies, published in Friday's issue of the journal Science, may take doctors a step closer to understanding whether leptin could be manipulated to help overweight people lose weight and keep it off.
The findings might also help explain why the food a person eats when very young, or even what a mother eats while pregnant, affects weight, heart disease and other aspects of metabolism later in life.
And they shed some light on why it is so hard for many people to lose weight and keep it off.
In one study, a team at the Howard Hughes Medical Institute and Rockefeller University and at Yale University, found that leptin affects both the physical structure and the function of neural circuits in the brain.
"This is a very dynamic effect that's quite dramatic and somewhat surprising. In response to leptin, the cells create new connections," said Rockefeller's Dr. Jeffrey Friedman.
"The malleability of these feeding circuits by leptin suggest the possibility that the brain's wiring may be different in lean versus obese individuals," Friedman added in a statement.
The researchers worked with specially bred mice, but when it comes to basic biology, mice are very similar to humans.
When it was discovered in 1994, leptin thrilled scientists because it seemed so basic to obesity and appetite. Overweight rodents fed leptin lost weight and studies quickly showed that some overweight people had unusually low levels of the hormone.
But leptin's effect was not so straightforward in humans, and it became clear that simply injecting obese people with it was not going to make them lose weight.
In a second study, scientists at Oregon Health & Science University found exposure to leptin early in life affected brain structures involved in weight regulation.
Also working with mice, Richard Simerly and colleagues tracked development of neurons in a part of the brain called the arcuate nucleus of the hypothalamus.
Brain circuits there were less developed in mice genetically engineered to make no leptin compared to normal mice. Injecting leptin-lacking baby mice with leptin restored normal brain structure, they found.
"We're excited about this finding because it shows how exposure to leptin can directly affect development of brain structures involved in regulating body weight," Simerly said in a statement.
"Our findings suggest a link between the developmental actions of leptin and early onset obesity," he added.
"We were shocked by how clear the result was. Leptin plays an important role in brain development, by acting specifically on the clusters of brain cells that regulate food intake."
The findings may help explain how some people seem to have a body weight "set point" - "until now a nebulous concept in search of a mechanism," said Joel Elmquist and Jeffrey Flier of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.
The findings support "the concept that under- and over-nutrition during critical periods of hypothalamic (brain) development may induce long-lasting and potentially irreversible effects into adulthood," they wrote in a commentary in Science.
SOURCE: Science, April 2, 2004.
Reuters Health
By Maggie Fox
Friday, April 2, 2004
WASHINGTON (Reuters) - Leptin, a hormone that affects weight and appetite, apparently helps wire the brain in ways that might set an animal on a lifetime path to slenderness or obesity, two teams of U.S. researchers said on Thursday.
The studies, published in Friday's issue of the journal Science, may take doctors a step closer to understanding whether leptin could be manipulated to help overweight people lose weight and keep it off.
The findings might also help explain why the food a person eats when very young, or even what a mother eats while pregnant, affects weight, heart disease and other aspects of metabolism later in life.
And they shed some light on why it is so hard for many people to lose weight and keep it off.
In one study, a team at the Howard Hughes Medical Institute and Rockefeller University and at Yale University, found that leptin affects both the physical structure and the function of neural circuits in the brain.
"This is a very dynamic effect that's quite dramatic and somewhat surprising. In response to leptin, the cells create new connections," said Rockefeller's Dr. Jeffrey Friedman.
"The malleability of these feeding circuits by leptin suggest the possibility that the brain's wiring may be different in lean versus obese individuals," Friedman added in a statement.
The researchers worked with specially bred mice, but when it comes to basic biology, mice are very similar to humans.
When it was discovered in 1994, leptin thrilled scientists because it seemed so basic to obesity and appetite. Overweight rodents fed leptin lost weight and studies quickly showed that some overweight people had unusually low levels of the hormone.
But leptin's effect was not so straightforward in humans, and it became clear that simply injecting obese people with it was not going to make them lose weight.
In a second study, scientists at Oregon Health & Science University found exposure to leptin early in life affected brain structures involved in weight regulation.
Also working with mice, Richard Simerly and colleagues tracked development of neurons in a part of the brain called the arcuate nucleus of the hypothalamus.
Brain circuits there were less developed in mice genetically engineered to make no leptin compared to normal mice. Injecting leptin-lacking baby mice with leptin restored normal brain structure, they found.
"We're excited about this finding because it shows how exposure to leptin can directly affect development of brain structures involved in regulating body weight," Simerly said in a statement.
"Our findings suggest a link between the developmental actions of leptin and early onset obesity," he added.
"We were shocked by how clear the result was. Leptin plays an important role in brain development, by acting specifically on the clusters of brain cells that regulate food intake."
The findings may help explain how some people seem to have a body weight "set point" - "until now a nebulous concept in search of a mechanism," said Joel Elmquist and Jeffrey Flier of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.
The findings support "the concept that under- and over-nutrition during critical periods of hypothalamic (brain) development may induce long-lasting and potentially irreversible effects into adulthood," they wrote in a commentary in Science.
SOURCE: Science, April 2, 2004.
