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Mouse Study Implicates Brain Enzyme in Obesity
> 5/7/2008 1:06:19 PM

In a new study from the May issue of Cell Metabolism, researchers from Duke University Medical Center further our understanding of the mechanisms that may underlie the drive to eat. Using mice, they examined how CaMKK2, an enzyme found in the hypothalamus, fits into a network of molecular factors that influence hunger and eating habits. Their findings indicate that when CaMKK2 is blocked or absent, mice maintain a healthy weight and are less likely to develop diabetes.

Research into obesity has identified many factors involved in appetite, and CaMKK2 may be an important element of this network because it stimulates AMPK, an enzyme that regulates cellular energy and has been shown to affect food intake. In their study, the researchers found that mice lacking CaMKK2 have less AMPK activity. In addition, while normal mice will eat more and after being administered ghrelin, a hormone that creates the urge to eat, this hormone had no effect on the eating habits of mice missing CaMKK2.

To more directly examine CaMKK2's influence on hunger and appetite control, the researchers blocked the enzyme in normal mice and observed their eating habits in two different situations: after a two-day fast and over a period of six days. In both instances, mice missing CaMKK2 ate less and gained less weight than control mice. These changes in eating behavior corresponded with a drop in activity of neuropeptide Y, a peptide also involved in controlling the urge to eat. This may indicate that the mice ate less because their appetites were reduced.

The researchers next investigated the effect of a high-fat diet on both normal mice and mice without CaMKK2 over the course of 31 weeks. Normal mice gained more weight regardless of whether the mice had been fed a diet low in fat or high in fat. When further testing was conducted after the mice had been eating high-fat diets, the differences between the two kinds became more evident. Normal mice were more likely to develop glucose intolerance and insulin resistance, symptoms of diabetes. In contrast, mice missing CaMKK2 responded to glucose and insulin as though they had been fed a low-fat diet, and this finding suggests that blocking CaMKK2 may protect against diabetes.

A better understanding of how various mechanisms affect hunger and eating habits may lead to effective treatments for obesity and its associated conditions, and the researchers of this current study say that further investigation of their findings may lead to new ways of treating diabetes. Lifestyle changes remain vital steps for improving health, but as researchers continue to examine obesity and the factors that contribute to it, they may discover new treatment options for those whose weight has become unmanageable and who are at risk for serious health conditions.

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