Learning to control energy balance
1 November 2007
Keeping the body’s energy resources balanced is key in maintaining health at both individual cell and whole body level. Problems in maintaining energy balance, a process called homeostasis, can cause development of metabolic diseases like type 2 diabetes.
Researchers led by Dr David Carling of the Cellular Stress Group at the Medical Research Council Clinical Sciences Centre have recently studied the molecular basis for energy balance in an attempt to develop new strategies to combat metabolic diseases. The results are published in The Journal of Biological Chemistry.
The team focused on A-769662, a small molecule that is known to have beneficial effects on the metabolism of obese mice. They have figured out how A-769662 activates a larger molecule called AMPK which is understood to regulate body energy in response to signals from hormones and the presence of nutrients, as well as in response to exercise.
When AMPK is activated the symptoms of some conditions lessen; as a result it is already being targeted in attempts to develop treatments for illnesses linked to metabolism.
This new knowledge of precisely how A-769662 works is important in understanding how to make the AMPK molecule active and so potentially correct the energy imbalances that cause disease.
Dr Carling said: ‘‘Despite efforts to design therapies that use AMPK there has been little progress in identifying molecules that actually get it working. By showing how A-769662 works to activate AMPK we have demonstrated that it is possible to find ways of achieving this. It may lead to discovery of other activator molecules and eventually to successful therapies for metabolic diseases.’’
Original research paper: Defining the mechanism of Activation of AMP-activated Protein Kinase by the Small Molecule A-769662, a Member of the Thienopyridone Family is published in The Journal of Biological Chemistry.
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