The regulation of food intake and eating behavior is vital to the survival of the human species. Along with getting enough food to provide the energy we need to carry out all the bodily processes that consume energy 24/7 such as thinking, pumping of the heart, skeletal muscle work, filtration and concentration of urine, detoxification that goes on in the liver and cell growth and repair, the body must maintain homeostasis which means it must carefully regulate temperature, water balance, reproduction and control stress (to name a few vital body functions). The control center for all of these processes is a tiny and evolutionarily ancient region of the brain called the hypothalamus. Different groups of nerve cells (called neurons) clustered throughout the hypothalamus are tasked with coordinating and regulating these processes.

As such, there exist centers in the hypothalamus that also regulate feeding behavior -- making us hungry and also telling us when we have consumed enough food. A simple analogy might help you understand the process. Insects basically have no fat cells, so the food they eat is stored in their gut until it is absorbed and enters the blood, where it travels throughout the body and is taken up by cells and turned into energy. Hence, food is metabolized into the energy currency of life -- ATP. ATP may then be broken down and used to fuel all the processes that have been mentioned, or it may be stored for future use, much like dollars in the bank. After eating, when their gut is full a nerve signal is sent from the gut to the brain that tells the insect to stop eating -- essentially the "I am full" signal. This is sort of a brain-belly connection in the insect world. If that nerve is cut, insects will literally eat until their gut explodes because they haven't been told that they are "full" since the nerve that delivers that signal has been cut. It works like a feedback loop. They eat, trigger the nerve and the nerve says "I'm full, stop eating." When their stomach is empty, the nerve stops sending the "full" signal and they start eating again.

This is how insects meet their energy needs and control how much they eat. We work sort of the same way except we have fat cells that act as an additional storage depot for energy. So we have our own brain-belly connection and another brain-fat tissue connection (adiponectin and leptin being examples of the latter). In addition, we have the endocrine system that plays a role by keeping all the systems of the body on the same page when called on to react. This system includes insulin, glucagon and thyroid hormone as examples.

Gut hormones play a role in the brain-gut axis including ghrelin and PYY. There are also signaling molecules in the brain (where they are called neurotransmitters) that include NPY (neuropeptide Y) and Agouti-related protein (AgRP). As you can see there is a real potpourri of names and compounds in this complex food/energy regulatory system.

The best way to understand how the system works is to ask yourself what it is really designed to do. The answer to that question is pretty simple. It is to make sure each cell in the body has the energy (generated from food nutrients) to perform its task. The hypothalamus coordinates this by functioning as the central clearing house of energy information. What that means is that specific nerve cells in the hypothalamus act as energy sensors for the body. When they are short on fuel/energy, they assume the rest of the cells in the body are as well and generate a hunger signal. When they sense no energy shortfall, the hunger signal stops.

So what constitutes the hunger signal in the nerve cells in the appetite-regulating centers of the hypothalamus? Good question. The best information available implicates a funny sounding molecule and an enzyme that helps regulate that molecule. When the concentration of the molecule (which signals that energy is either plentiful or in short supply) moves up or down, the variation is sensed by the enzyme that monitors it. This produces a change in activity of that enzyme. When the enzyme is turned on or off, it triggers changes in neurotransmitters such as NPY -- the hunger signal that tells the brain to get hungry and eat.

The energy molecule is called Malonyl CoA and the enzyme is called AMP Kinase (short for Adenosine Mono-Phosphate Kinase). Here the chemistry can get pretty complicated but to really know what is going on we'll go through a brief description.

The brain burns glucose. So when this happens glucose in the neurons in the appetite centers of the hypothalamus metabolize it to a compound called citrate which is metabolized to Malonyl CoA. When Malonyl CoA levels build up, the neuron starts synthesizing fat for storage (using the Malonyl CoA) and stops breaking down fat for energy because it has all that it needs. That's why Malonyl CoA is called the "signal of plenty" and when it builds up there is a concomitant fall in AMP Kinase activity. When this happens,  NPY levels fall and our appetite decreases.

When glucose is scarce, Malonyl CoA levels fall, AMP Kinase is turned on, NPY levels rise and we get hungry. So it is similar to the brain-belly feedback loop in insects.

Now what about Ghrelin and the other gut and fat hormones we have mentioned? Well, most of them are secreted into the blood, float around until they bind to receptors in the appetite centers in the hypothalamus and when this happens they either increase or decrease the activity of AMP Kinase which further modulates all the signals and tells us how hungry to be at any particular time. But the basic idea revolves around whether there is enough energy for the cells in the body. The entire appetite regulating system has many redundancies and much complexity but that is how it works.

From a hunger prevention perspective, you can now see why if you feed your brain appropriately by consuming slow-release carbs (that contain fiber and are less likely to produce subsequent dips in blood sugar (which are sensed by the nerves in the appetite centers of the brain and trigger hunger responses)) you will avoid stimulating your appetite centers. Compare this with what happens when sugars and other rapidly absorbed carbohydrates are consumed. They generate a high sugar spike in the blood and a subsequent abrupt fall in glucose levels which is sensed by the brain and generates a hunger signal. In addition, by choosing healthy fats (such as flax oil, coconut oil and mono-unsaturated fats) that are easily turned into energy and keep the brain happy for hours, you easily keep hunger at bay. This is the best way to keep the brain happy and lose weight at the same time!