Born To Overeat

Kim Tingley covers Prader-­Willi syndrome:

In 1981, researchers at the Baylor College of Medicine made a significant discovery: Errors on the chromosome 15 segment — which occur at conception and for which there are no clear risk factors, except in a fraction of cases — produce the syndrome, making it one of few known genetic causes of obesity. No other genetic disorder incites the same extreme lack of satiety or urge to obtain food. Researchers now know that the damaged stretch of chromosome affects at least a dozen genes, but which of those genes govern hunger and fullness — and how — is still a mystery. What is certain is that Prader-­Willi disrupts the functioning of the hypothalamus, a region of the brain that is involved in appetite control.

One result is a heightened, permanent sensation of hunger. “They describe it as physical pain,” Jennifer Miller, an endocrinologist at the University of Florida who treats children with Prader-­Willi, told me. “They feel like they’re going to die if they don’t get food. They’re starving.” Parents must lock their pantries, refrigerators and trash cans, and their children frequently lie and steal to get something to eat.

The syndrome “could offer universal truths about the biology of hunger and fullness”:

Researchers believe that hundreds of genes, combined with environmental factors, have the potential to influence whether a person in the general population overeats and how easily he or she gains weight. But in almost all cases of obesity, the body eventually fails to properly process leptin, a hormone produced by fat cells. Leptin and other hormones signal the hypothalamus to prompt you to eat or alert you that you’re full, but in obese people these systems break down, preventing them from feeling sated. In some cases, including Prader-­Willi, resistance to leptin appears to come first, leading to insatiability and weight gain. In others, the reverse happens: Weight gain causes resistance to leptin, which increases appetite and perpetuates the cycle. “As people gain weight, they inflict a chronic injury to the hypothalamus — to the cells in the brain that sense whether their body weight is appropriate,” says Rachel Wevrick, a professor of medical genetics at the University of Alberta who studies Prader-­Willi. …

Robert Nicholls, a geneticist at the Children’s Hospital of Pittsburgh who studies Prader-­Willi, believes it is “very unlikely” that our species evolved multiple, separate systems to govern eating. Understanding why people with Prader-­Willi switch in early childhood from an extreme lack of interest in food to insatiability could offer clues about the nature of appetite — which might eventually help scientists minister to a person’s specific type of overeating or prevent it altogether. It’s possible that it could do the same for conditions of undereating and malnutrition, like anorexia. Whether damage to the hypothalamus can be undone at all, regardless of its cause, is still an open question, but one that a successful treatment for Prader-­Willi could answer.