Metabolic Disease: AMPK Keeps Energy Balance Steady

One aspect of such research is understanding how the brain controls these processes. Expression of the protein AMPK in neurons in the brain has been suggested to be important for regulating energy balance, but in which neurons its expression is important was not clear.

To address this issue, Dominic Withers and colleagues from University College London, United Kingdom, generated mice lacking AMPK function in either POMC neurons or AgRP neurons. As reported in the August issue of the Journal of Clinical Investigation mice lacking AMPK function in POMC neurons became obese because they reduced their energy expenditure and increased their food intake after fasting.

By contrast, mice lacking AMPK function in AgRP neurons showed age-dependent decrease in body weight. Surprisingly, these effects were mediated by an inability of the neurons to respond to changes in glucose levels and not caused by impaired responses to the hormone regulators of energy balance leptin and insulin. These latter observations, that AMPK is only required for the response of POMC and AgRP neurons to some signals that regulate energy balance led the authors to conclude that AMPK is "not a general sensor and integrator of energy homeostasis in the hypothalamus."

The surprising nature of the results is discussed further in an accompanying commentary by Joel Elmquist from the University of Texas Southwestern. Elmquist notes that it is complex studies such as these that uncover unexpected results that are "needed to combat the growing problems that are obesity and diabetes."

 AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons