Sci. Aging Knowl. Environ., 15 June 2005
Vol. 2005, Issue 24, p. nf45
[DOI: 10.1126/sageke.2005.24.nf45]


Premature Emission

Early surge in fat-fighting hormone might trigger obesity later in life

Mitch Leslie

An actor who misses his cue can spoil a scene. Timing is equally important to keep metabolism running smoothly, according to a new study. The work suggests that a premature jump in the hormone leptin soon after birth boosts susceptibility to obesity later in life. The results might help explain why babies whose mothers are undernourished often grow into hefty adults.

A mother's influence on her offspring can last a lifetime, particularly if she doesn't get enough to eat during pregnancy (see "From Womb to Tomb"). According to the fetal origins hypothesis, calorie shortages in the womb hike the odds of developing diseases later in life. Supporting that notion, small babies, who often have endured poor prenatal nutrition, are prone to heart disease as adults. Further work has linked maternal undernutrition to obesity, high blood pressure, abnormal concentrations of blood fats, and other metabolic foul-ups later in life. Researchers have identified several possible mechanisms for how events during pregnancy spur metabolic problems years afterward, including stress (see "From Womb the Bell Tolls"). One possible contributor is leptin, a metabolism-regulating hormone that quells appetite and boosts energy use. Production of leptin surges in mice shortly after birth, and endocrinologist Norimasa Sagawa of Kyoto University in Japan and colleagues wanted to determine whether changes in this burst influence the response to earlier food scarcity.

The researchers first confirmed that slashing rations for pregnant mice predisposes their offspring to obesity. If the pups ate a high-fat diet, they packed on extra weight; mice from normally fed moms stayed lean. The leptin pulse peaked about 6 to 8 days sooner in progeny from undernourished mothers than in young of well-fed females, the researchers found. To determine whether the early burst was sufficient to make mice plump, they injected the hormone into pups from mothers who'd had plenty of chow. The dosed mice grew normally if they ate regular rodent food, but on a high-fat diet they became tubby and amassed extra blubber. Fat cells produce leptin, which travels to the brain and prods the hypothalamus, the region that regulates appetite and metabolism. The team determined that early leptin surges hinder leptin from entering the brain, possibly by reducing the amount of a receptor that allows the hormone to cross the blood-brain barrier. Premature pulses also boosted the number of neurons in the hypothalamus that carry two other hunger-regulating proteins, indicating that the leptin burst modifies the composition of the hypothalamus. Overall, the work suggests that leptin pulses soon after birth adjust metabolism, priming the animals for obesity.

"It's a neat, new hypothesis for how prenatal undernutrition hardwires appetite and metabolism in the hypothalamus," says endocrinologist Jonathan Seckl of the University of Edinburgh in the U.K. The results suggest that the early leptin burst reorganizes the brain, which could explain how it revamps metabolism, says developmental physiologist Peter Nathanielsz of the University of Texas Health Science Center in San Antonio. Future studies might reveal whether improving leptin's timing could prevent an early curtain for some people.

June 15, 2005
  1. S. Yura et al., Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell Metab. 1, 371-378 (2005). doi:10.1016/j.cmet.2005.05.005 [CrossRef][Medline]
Citation: M. Leslie, Premature Emission. Sci. Aging Knowl. Environ. 2005 (24), nf45 (2005).

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