Memory Study Leads to Obesity Finding; A Fat Storage Hormone Changed Minds and Weight of Study Mice

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Byline: JEREMY COX

Their mission was to solve a small but nagging mystery of Alzheimer's disease: How would the brain's ability to store information be affected if they "turned off" the obscure protein LRP1?

But Guojun Bu and his fellow researchers were in for a surprise. As they expected, mice whose brains had been wiped of the LRP1 gene showed Alzheimer's-like memory problems. But they also started to put on weight - fast.

The mice were lethargic. They were on their way to becoming diabetic. And they didn't seem to know when to stop eating.

In other words, they were a lot like the more than 72 million Americans who are obese.

Bu, a neuroscientist at the Mayo Clinic in Jacksonville and the study's lead author, said the findings could lead to a treatment that attacks the genetic causes of obesity.

"People complain that for people who are obese, it's just a lack of self control," he said. "But this confirmed there's a strong genetic element that controls their appetite."

Or rather, reconfirmed. Scientists have long suspected that people's DNA has a profound impact on their waistlines, and a number of studies have proved them right.

Bu's research focused on leptin, a hormone that regulates fat storage. Normally, leptin is produced as the body's cells take in fat from food, sending a signal to the brain that suppresses appetite. Bu, who did the bulk of the research while with the Washington University School of Medicine in St. Louis, found that both the leptin and LRP1 receptors must work together to transmit those signals.

Researchers injected a virus into young mice to turn off the LRP1 gene in the hypothalamus, the brain's control center. After six months, there was virtually no difference between the "knock out" mice and the normal ones.

But then, the modified mice suddenly got plumper as their leptin signals faded. A year into the experiment, the mice weighed an average of about 43 grams; their counterparts, less than 30. …