That little voice inside your head that tells you to keep eating is, in fact, simply a cluster of around 10,000 brain cells. Now scientists believe they have found tiny triggers inside those cells that give rise to this 'voice' and ruin a dieter's good intentions. The new research, done on fish and mice, could someday lead to pills that will be able to quieten that voice or increase its volume. The research focused on POMC neurons, which are a structure called the hypothalamus, that send and receive signals to regulate appetite. On the left, images of normal hypothalamus POMC cells from a developing mouse. On the right: when the gene for the transcription factor is deleted, the cells no longer make it . The research focused on POMC neurons, which are a structure called the hypothalamus, that send and receive signals to regulate appetite. When POMC neurons are absent, or not working properly, animals and humans grow dangerously obese. The new findings show in animals that the same thing happens when certain genetic triggers inside the POMC cells aren't working. The team, led by the University of Michigan, looked at how a protein called a transcription factor, and two small stretches of DNA called enhancers, act as triggers for the Pomc gene. All three regulate how often and when the POMC cells use the gene to create the signal molecules that then go out to the body. That little voice inside your head that tells you to keep eating is, in fact, simply a cluster of around 10,000 brain cells. Now scientists believe they have found tiny triggers inside those cells that give rise to this 'voice' 'The POMC region is a central node of the brain's means for regulating body weight, in response to influences from the hormone leptin,' said Malcom Low, a professor in the Department of Molecular and Integrative Physiology. Like signal lights that show pilots the path to an airport runway, enhancers guide proteins toward the gene so it can be read. Located deep inside the brain, in a structure called the hypothalamus, the cluster of POMC neurons act as a control center for feelings of fullness or hunger. They take in signals from the body, and send out chemical signals to regulate appetite and eating. When POMC neurons are absent, or not working correctly, animals and humans grow dangerously obese. The latest research show in animals that the same thing happens when certain genetic triggers inside the POMC cells aren't working. The researchers found that the two enhancers act in ways that complement one another, both encouraging the expression of the Pomc gene at key times. Mice born without both of them became obese – as if their Pomc gene had been deactivated. The protein that latches on to the enhancer, called a transcription factor, is also vital. In the new PNAS paper, the researchers report that the transcription factor Islet 1, encoded by the Isl1 gene, plays this important role for POMC. When the researchers blocked cells of the hypothalamus from making Islet 1 halfway through pregnancy, the fetal mice failed to develop any POMC cells. 'Taken together, this work represents the first example of a neuron-specific gene in vertebrates where we have found both the enhancers and a shared transcription factor that control gene expression in the developing brain and then throughout the life span of the adult,' says Low. Looking to see if the same factors do the same thing in humans will be more complex – and there may be other enhancers and transcription factors involved. But in theory, it could be possible to find drugs to increase the production of Pomc gene products, or to help silence it. 'For humans, Pomc regulation may be part of the equation of weight control,' says Low. 'We don't know, but we think it likely, that it may be similar to the mouse model, where its role is like a dial, with a linear relationship between the amount of Pomc expression and the degree of obesity.'
The research looked at POMC neurons that work toregulate appetite . When POMC neurons are absent, animals and humans grow obese . This also happens when genes inside the POMC cells aren't working .