Hormone boosts metabolic rate, induces weight loss in mice

Science News, April 17, 2004 by John Travis

When injected into the brains of mice, a hormone produced by fat cells induces the animals to burn more energy than normal and lose weight, according to a new study. The finding bolsters the view that body fat carries on a complex chemical conversation with the brain, one that physicians might tap into to treat obesity and other weight disorders.

Until a decade ago, scientists largely viewed fat cells, or adipocytes, as mere sacs of fat. Then leptin made its surprising debut. Researchers found that this hormone is secreted by fat cells and recognized by brain regions that control food intake. Some people hailed leptin as the key to defeating obesity.

Although that early enthusiasm faded as experiments failed to show a role for leptin in most human obesity, the hormone's discovery set the stage for a reassessment of fat cells. They've since been found to secrete several additional chemicals, including adiponectin, the subject of the new study.

Past experiments had shown that adiponectin regulates how readily muscle burns fatty acids for energy and influences how the liver responds to blood sugar.

Working with muscle and liver tissue, a Japanese research group recently identified cell-surface proteins that bind and respond to adiponectin. Pharmaceutical companies now view the hormone as a potential drug for diabetes.

However, Rexford S. Ahima of the University of Pennsylvania School of Medicine in Philadelphia has suspected since adiponectin's discovery that it might also target the brain, as leptin does. In an upcoming Nature Medicine, he and his colleagues offer evidence supporting that view.

In one experiment, he and several coinvestigators injected the hormone into the blood of mice and tracked its concentration in the fluid that bathes the brain and spinal cord. "We were able to detect a clear increase in the cerebrospinal fluid,' says Ahima.

In a subsequent experiment, the researchers injected small amounts of adiponectin directly into the brains of mice. The treated animals lost weight over the next few days. Those receiving the largest amount of adiponectin showed the greatest slimming. Mice in that group lost an average of about 5 grams, or one-fifth their starting body weight.

The mice receiving adiponectin injections into their brains didn't appear to become sick or eat less than mice getting similar injections of a saline solution did. Ahima's team found that the hormone-treated mice burned more energy than the others. This boost in metabolic rate appears to explain the weight loss, says Ahima.

Adiponectin's influence on metabolism but not on eating is a "very interesting observation," says Luciano Rossetti of the Albert Einstein College of Medicine in New York. Whether adiponectin naturally regulates body weight, however, is controversial. Several groups have created mice lacking the hormone, and the animals aren't noticeably thinner or heavier than normal, Rossetti points out.

Given leptin's rise and fall, Ahima also declines to tout adiponectin as the next weight-loss drug. He does note that dieters often regain pounds because their bodies respond to weight loss with lowered metabolism. An adiponectin-based drug could, in theory, raise a dieter's metabolic rate back to normal. "This would be a nice way to sustain weight loss," says Ahima.