By LEE BOWMAN
Scripps Howard News Service
June 07, 2005
A study published Tuesday in the journal Cell Metabolism suggests that a premature surge of the hormone in newborn pups of underfed mouse mothers leads to a remodeling of key brain circuits that contribute to obesity in the animals later in life.
Leptin is a hormone produced by fat that normally decreases appetite and food intake and increases energy expenditure. In many species, including humans, the hormone acts to stabilize weight and glucose balance through its effects on leptin receptors in the brain's hypothalamus.
The new findings lay out one mechanism of how metabolic disease can originate from early developmental experiences starting in the womb, the researchers said.
"Obesity has increased at an alarming rate in Western countries and is now a worldwide public health problem," said Shingo Fujii, senior author of the study and a researcher at Kyoto University Graduate School of Medicine. Both genetic and environmental factors, such as a high-calorie diet, are thought to contribute to the prevalence of obesity.
Earlier research has shown that mice lacking leptin quickly become obese, but this condition can be reversed with leptin treatment. However, obese animals often exhibit resistance to leptin's usual effects, even with high concentrations of the hormone. Studies have also shown that leptin levels before birth play a key role in how energy-regulating circuits in the brain are formed.
"The present study suggests that a premature surge of leptin as a result of fetal undernourishment can alter energy regulation by the brain and contribute to developmental origins of health and disease," Fujii said.
In the study, mice born to mothers that ate 30 percent less than normal were small at birth and had less fat. But the undernourished newborns caught up with normal mice in weight after 10 days, and, when fed a high-fat diet, developed pronounced weight gain and increased leptin levels compared to the normal mice on the same diet.
The undernourished mice had lower body temperatures than normal mice, suggesting that the prenatal nutritional shortfall had "programmed" them to conserve energy, the researchers said.
During the catch-up growth period, the short-term rise in leptin levels that are normally seen in newborns occurred six to eight days earlier in the undernourished animals.
When the researchers mimicked that premature leptin surge by injecting the hormone in normally fed mice, they too became prone to obesity when they were given a diet high in fat.
"Unexpectedly, normal offspring treated with leptin as newborns were indistinguishable from those that were undernourished before birth," Fujii said. This implies that the premature surge of leptin triggers obesity in undernourished offspring, and that the surge may be a target for some type of medical intervention that could head off early developmental changes that set kids up for obesity early in their lives.
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