Got an appetite? Slow down the right enzyme in the neurons!
Scientists at Duke University (Durham, North Carolina), working under the guidance of Professor Tony Means, claim that they have identified an important therapeutic target – the enzyme of brain cells CaMKK2 (calcium/calmodulin-dependent protein kinase kinase 2), exposure to which will simultaneously control appetite, reduce weight and improve carbohydrate metabolism.
For many years, scientists have been identifying and testing each link of the mechanisms of stimulation and suppression of appetite. The aim of this work is to find an opportunity to help people who want to lose weight and minimize the risk of developing diabetes, heart disease and other obesity-associated pathologies.
Activation of the CaMKK2 enzyme is one of the stages of the appetite stimulation mechanism associated with the hypothalamus. The work of this mechanism begins with the hormone ghrelin synthesized by an empty stomach, which triggers a complex cascade of signals, eventually leading to a feeling of hunger.
The authors suggested that CaMKK2 is a worthy object for study, because it activates adenosine monophosphate kinase (AMPK), an enzyme that stimulates the consumption of more food and weight gain.
The researchers tested their hypothesis in three series of experiments. First, they blocked CaMKK2 in the brains of mice using a specialized inhibitor molecule and assessed changes in the amount of food consumed by animals. During the six days of observation, such animals ate significantly less than the animals of the control group, and at the same time lost weight.
After that, the scientists tested the effect of the CaMKK2 inhibitor on lines of genetically modified mice unable to synthesize this enzyme. The absence of any recorded changes served as proof that the CaMKK2-mediated mechanism is very important for appetite management.
As part of the third series of experiments, scientists analyzed the reactions of ordinary and transgenic mice to diets with low and high fat content. Approximately 30 weeks of being on a fat-rich diet was enough for normal mice to develop insulin resistance and diabetes, while a low-fat diet did not have a negative effect on their health. At the same time, mice lacking the CaMKK2 enzyme remained healthy regardless of the type of diet.
The authors also note that blocking the activity of the enzyme CaMKK2 in the brain prevents the accumulation of fat in the liver and skeletal muscles, characteristic of patients with obesity and diabetes. Currently, they are engaged in deciphering the mechanisms that cause this effect and searching for more effective drugs-inhibitors of CaMKK2.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
12.05.2008