Tony Means, PhD, and his team at the Duke University Medical Center were able to tone down appetite and promote weight loss, while improving the body’s ability to handle blood sugar levels, when they blocked a brain enzyme, CaMKK2, in mice.
“We believe we have identified an important drug development target that could potentially turn into a metabolic triple play: appetite control, weight loss and blood sugar management,” said Means, who is the Nanaline H. Duke Professor and Chairman of Pharmacology and Cancer Biology.
For many years, scientists have been identifying and testing every step of the appetite stimulation and suppression pathways in search of a target. Such research is considered critical to finding ways for people to better control their weight and minimize their risk of developing diabetes, heart disease and other health conditions. Activation of the enzyme CaMKK2 is just one step in the appetite stimulation pathway located in the hypothalamus section of the brain. An empty stomach releases the hormone ghrelin, which launches a cascade of signals that ultimately results in increased appetite.
Means and colleagues believed that CaMKK2 in the ghrelin pathway might be a likely candidate for study, because it activates AMPK, an enzyme that stimulates animals to eat and gain weight. They tested their theory in several ways, the results of which are published in the May issue of Cell Metabolism. The work was funded by NIH grants, as well as by the Australian Research Council, National Heart Foundation and the National Health and Medical Research Council of Australia.
First they blocked CaMKK2 in mice with a specialized molecule inhibitor and then measured food intake. These mice ate significantly less food than untreated mice during the six days in which they were evaluated, and also lost body weight, which led the scientists to think they might be on to something. Next they studied a group of mice that normally do not make CaMKK2 and found that the molecule inhibitor did not change feeding behavior or reduce weight. “The fact that blocking CaMKK2 worked in normal mice to make them eat less and lose weight, but not in mice missing the enzyme, provides compelling evidence that CaMKK2 signaling is a requirement for appetite control,” Means said.
Release date: May 6, 2008
Source: Duke University Medical Center