Weighty from the womb? Early exposure to leptin may program mice to become obese adults.

An Early Trigger for Obesity

For some people, no matter how much they diet or exercise, the kilograms come more quickly than they go. New research on mice places at least some of the blame on early exposure to a protein called leptin, which may program some infants to cling to calories others burn easily.

Babies born on the small side are more likely to be overweight as children and adults. Some researchers suspect the problem may lie with a metabolic program that is set before birth. Babies who receive poor nutrition in the womb, the theory goes, can expect to face food shortages after birth as well, and their metabolism is programmed to be especially thrifty with the calories they do receive. When such individuals eat the high-fat diets typical in today's developed countries, they quickly become overweight.

The biological mechanisms that might program this thrifty metabolism are far from clear. Gynecologist Norimasa Sagawa of Kyoto University Graduate School of Medicine in Japan and his colleagues wondered if the protein leptin might play a role. Leptin helps regulate metabolism by triggering the feeling of being full, and recent studies have shown it also figures in brain development (ScienceNow, 2 April 2004). Could leptin be affected in low-birthweight mice? Sagawa and colleagues compared mice whose mothers had received 30% fewer calories during pregnancy with normal controls and found that the underweight pups experienced a shift in timing: the normal increase in blood leptin a week earlier than usual. And, consistent with other studies, when these mice ate a high-fat diet, they gained weight faster than their normal counterparts.

The researchers were also able to turn normal-birthweight pups into obese mice by injecting extra leptin 5 to 10 days after birth. The premature surge of leptin may be altering the development of the hypothalamus, a region of the brain that helps to regulate appetite and metabolism, say the researchers, who report their findings today in Cell Metabolism.

It's not clear how relevant this is to humans. For starters, no one knows whether this leptin surge occurs at all in infants, says pediatric endocrinologist Ken Ong of the University of Cambridge in the United Kingdom. However, he says, observing the leptin levels in infants and young children may lead to important clues about the causes of adult obesity. Finding a way to keep levels of leptin under control in small babies, says Sagawa, might save them hours on the treadmill years later.

Related site
Howard Hughes Medical Institute story on Leptin and its discoverer Jeffrey Freidman