The enzyme link to slim waistline
Blocking a brain enzyme could help in appetite control, weight loss and blood sugar management, says study.Updated: May 08, 2008, 18:00 IST
Just by blocking a brain enzyme, medical scientists reduced appetite and prompted weight loss, even as the blockage improved the body's ability to handle blood sugar levels.
"We believe we have identified an important drug development target (enzyme CaMKK2) that could potentially turn into a metabolic triple play: appetite control, weight loss and blood sugar management," said Tony Means of Duke University, who led the research.
For many years, scientists have been testing every step of appetite stimulation and suppression pathways, to help people control weight and minimise risk of diabetes, heart disease and other conditions.
An empty stomach releases the hormone ghrelin, which launches a cascade of signals. Then CaMKK2 in the ghrelin pathway activates AMPK, an enzyme that stimulates animals to eat and gain weight.
When scientists blocked CaMKK2 in mice with a specialised molecule inhibitor, they found the rodents ate significantly less than untreated mice during a six-day trial, and also lost body weight, which looked encouraging for scientists.
"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 signalling is a requirement for appetite control," Means said.
They also studied both normal mice and mice missing CaMKK2 to learn how these types responded to low-fat and high-fat diets.
After nearly 30 weeks on the specific diets, the normal mice on the high-fat diet became diabetic - they were unable to respond to insulin and weren't able to manage blood sugar levels well. Normal mice on a low-fat diet stayed healthy.
"Remarkably, we find that blocking CaMKK2 prevents deposits of fat in liver and skeletal muscle that are characteristic of obese, diabetic patients," Means said.
These results were published in the May issue of Cell Metabolism.