A protein previously known to regulate signals of hunger to the brain has recently been found to play another role in appetite: instead of acting on neurons, it affects astrocytes, a specific cell type in the hypothalamus. This can lead to total upheaval of the lines of communication signaling hunger or satiety. These findings have implications for the treatment of obesity and eating disorders such as anorexia.
To eat or not to eat? (Credit: daniellehelm / Flickr)
It’s hard to conceive of, but everything we do is a result of brain activity. My fingers typing right now is a product of motor cortex activity, the memories I have are stored in my hippocampus. So, it should come as no surprise that feeding behaviour and appetite are also known to arise from activity in a specific brain area - in this case, the hypothalamus.
So, if we know which neurons in the brain are responsible for feeding and appetite, what’s holding back medicines that prevent overeating or ease the transition from anorexia? Why do we still have an incomplete idea of how the system works?
The answer may lie in the fact that we are looking just at neurons. Indeed, there are many other types of cells in the brain, and it’s only been in the past 15 years that researchers have really started studying these ‘glial’, or non-neuronal, cells. One of the main types of glial cells of the brain are astrocytes, and they make up approximately half of the brain by volume! If you imagined that this was because they have a very important function in the brain, you’d be right - astrocyte activity is imperative to a properly working brain.
To understand the job of an astrocyte, you might think of the brain as a big factory, and neurons as the machines in the factory. This would make astrocytes the factory workers, running around doing 500 different things to make sure everything is going smoothly. Astrocytes are important for providing structure to the brain, delivering nutrients to neurons, and protecting the brain from damage and infection, among various other tasks that keep our neurons alive and happy.
So what do astrocytes have to do with hunger? Well, it’s all about detecting the presence of a hormone called leptin - the “satiety” hormone. This tiny protein holds the key to questions of appetite and metabolism: it is made by fat cells after storing fat and was already known to act on the neurons of the hypothalamus to decrease appetite. This hormone is your body’s way of telling your brain that you’ve eaten and don’t need to eat any more.
(Credit: mst7022 / Flickr)
But, in addition to affecting the neurons of the hypothalamus, a new finding suggests that leptin acts on the astrocytes there, too. A recent study by Jae Geun Kim at the Yale University School of Medicine finds that if astrocytes are unable to detect leptin, havoc is wreaked on the hypothalamus. The astrocytes change shape, a phenomenon similar to their reaction to infection. The connections between neurons sending signals to the feeding control centers of the hypothalamus are completely rewired. Most interestingly, the mice in these experiments had highly unregulated feeding patterns, continuing to eat even when leptin levels were high and signaling that the mouse had eaten enough.
These results imply that astrocyte responses to leptin are as important, if not more so, to appetite and feeding as neuronal responses. Because we see rewiring of the connections to the hypothalamus, these results also imply that while neurons respond to leptin quickly to signal whether it’s time to eat or not, astrocytes respond to leptin on a much larger scale, actually changing the system of the neuron’s communication. Much like a complex system of railroads, leptin affects neurons to signal when trains should leave the station, but an astrocyte’s response to leptin is to upheave the rails altogether.
The increasing occurrence of obesity and eating disorders worldwide has placed a strong emphasis on the importance of research concerning metabolism, food, and eating behaviours. Kim’s findings in particular suggest reasons why people suffering from anorexia have such difficulty readjusting to a healthy diet - after such little exposure to leptin, the astrocytes of these patients have rewired their hypothalamus to produce long-lasting changes. Understanding neural mechanisms of hunger and satiety are the first steps to providing effective treatments to those who suffer from such debilitating conditions, and will inform these patients, as well as the rest of the public, of the best actions to take in response to them.
About the author:
David Davila (@cozyneuroses) is a Master 2 student studying neuroscience in the program Approches Interdisciplinaires du Vivant. He recently won runner-up and audience choice prizes in the international science communication competition, Famelab, and is co-host of a new neuroscience podcast called “Brain Drain”.