I hate to say it this way, but homeostasis is a very important idea in biology.
If you’re anything like me, as soon as you hear the words “a very important idea” your eyes are glazing over, and you’ve started wondering what to stream tonight.
But hang on, it’s true. It really is in this case. Homeostasis is so important to human biology that I think we should have been called Homeo sapiens. It’s that important.
It’s a very simple concept. Homeostasis just describes the processes whereby a biological organism maintains a stable internal environment.
All these processes have the same general mechanism. There is a set point, or the desired state, there are sensors, that measure the current state, and there is some type of effector that monitors the sensors and takes action when the current state diverges from the set state.
It’s like when you are driving a car. If you are obeying the speed limit, you monitor the speedometer and you push down or ease up on the accelerator depending on how your current speed compares to the current limit.
The human body regulates lots of things in exactly this way. Temperature is an obvious one but things like blood pressure, oxygen levels, sleep and ion concentrations are all maintained using homeostatic processes.
As a consequence of this, just about every human disease involves the breakdown of some homeostatic process. Cancer, heart disease, high blood pressure and even mental illness can be explained as a breakdown in a homeostatic process.
Homeostasis also has a big part to play in whether your clothes from last year still fit. Yes, hunger is a part of the homeostatic processes that regulate our glucose levels and our weight.
Failures in these processes can lead to debilitating diseases like bulimia and anorexia and, if you’ve been wondering how the GLP-like peptides work? It’s by affecting these very same processes.
What is Hunger?
We all know what hunger is on a visceral level. Hunger is the compulsion to eat that we experience when we haven’t for a while.
This compulsion is mediated by a part of the brain called the hypothalamus. In response to blood borne signals from other parts of the body, the hypothalamus will release neurotransmitters that affect behavioural switches in the brain.
Hunger is one thing, but we also experience a feeling of fullness. Of having eaten enough food. This feeling of fullness, when we are loosening our belt and talking about food comas, is called satiation.
How hungry or sated we feel is ultimately mediated by the hypothalamus but the hypothalamus responds to several different homeostatic processes.
Gastric Accommodation
The first of these processes that contribute to how hungry we feel is called gastric accommodation. A feedback loop that acts to keep our gastric pressure low.
If you think about what happens when water is forced through a narrow tube. You have some idea of what the consequences of increased gastric pressure would be.
If the same thing happened when we ate food, the increased pressure would force food rapidly through our digestive system. Not only would we not have enough time to properly digest the food we would also have to deal with the consequences of a high pressure stream of semi-digested food wanting to leave the digestive tract. It would not be pretty.
Thankfully, our bodies are able to regulate gastric pressure.
Our stomach is the initial safeguard against gastric pressure. When we start eating our stomach can expand up to 15 times its normal volume. The stomach acts just like a dam. It accommodates the food and releases it slowly into the intestine. Making sure that downstream pressure never gets too high.
As our stomach expands, mechanoreceptors in the stomach sense the expansion and start signalling to our brain.
These signals travel via the vagus nerve and they not only initiate the slow release of food into the intestines but also the release of a whole bunch of hormones and regulatory molecules.
Molecules such as glutamate, gamma-aminobutyric acid (GABA), norepinephrine, CCK and glucagon-like peptide-1 (GLP-1) not only start to repress hunger but they also act to slow the rate of peristalsis (the rhythmic contractions that push food through our gut).
Apart from signalling from the brain our gut is also lined with cells that release signalling molecules in response to nutrients like proteins and fat.
These signalling molecules provide feedback as food passes through our gut that helps maintain an appropriate level of hunger, gastric pressure and gut motility. Effectively the nutrient composition of food in the intestines can influence upstream processes like gastric emptying. An example of this is the Ileal brake which is the name given to an inhibitory effect on gut motility and gastric emptying triggered by nutrients in the small intestine. The combined effect of all this signalling is not only the passage of food through our digestive system at an appropriate pressure and rate but also feelings of hunger, satiation and satiety in accordance with the processing status of our last meal.
Our progression through these stages is actually the result of several different, but connected, homeostatic processes, the contributions of which all sum to how we are feeling about eating at that particular moment. I’ve actually already covered one of these in the post on ultra-processed foods. The regulation of blood sugar levels is a homeostatic process that can contributes to how hungry we feel. But there are others that are just as important.
Although not overwhelming our system with excess food is one consideration, the real aim of eating is to maintain energy levels. So to tie in energy requirements the body has another feedback system which involves two hormones called ghrelin and leptin. A common strategy in the body is to have two molecules that act in opposing ways, we saw this with sleep regulation, and this is what is happening with ghrelin and leptin. Ghrelin is produced in the stomach and it’s levels increase as the stomach empties and it makes us hungrier. Leptin is released by adipose tissue, where fat is stored, in response to it’s fat levels and it represses hunger. The more fat stored by the body the more leptin adipose cells release. In the body the relative levels of ghrelin and leptin can influence how hungry we are and, along with our regulation of blood sugar levels, they are the way the amount of energy we have at hand contributes to how hungry we feel.
This is nothing but a rough sketch of hunger regulation in the body. The real story is a lot more complex and probably not completely worked out yet. The microbiome plays an important part in what is called the gut-brain axis and insulin is also important. There is also a lot of cross-talk between feedback loops; ghrelin for example is involved in insulin signalling among other things. Nonetheless this rough sketch helps us to understand why we get hungry but also what happens when things go wrong. Because, given our current obesity crisis, it’s obvious that things can go very wrong.
Ultra-processed foods get a lot of blame for obesity and armed with our model we can see why. I’ve covered the role of high sugar in UPFs and the insulin feedback loop but the structure of ultra-processed foods is also a potential problem. Because our hunger regulation is so intricately tied to the progression of food through our gastrointestinal tract the softness of UPFs, the lack of fibre needed to provide the raw bulk for gut motility, can confuse our feedback mechanisms. Our gastrointestinal tract is designed to process foods so if our food is pre-processed, so to speak, digestion and absorption of molecules will happen more quickly, our stomach will empty sooner and we end up hungry again despite the calories we have just eaten. If we eat a lot of UPFs, and in some western societies they make up 50% of the average diet, you can see how we can easily start overeating.
But people ate too much before UPFs though so we can’t blame everything on food companies. You can have a low fibre, high sugar and high fat diet without going anywhere near a UPF. This needs another post but speaking in general terms our bodies are tuned to scarcity, that is we evolved under conditions where highly calorific foods such as fats and sugars were relatively scarce. So when we encounter foods that are high in fats and sugars our body tends to make us very happy if we eat them, possible via dopamine secretion. So we ignore our bodies signals of satiety and keep eating because the pleasure of eating outweighs the discomfort.
In western countries, at least, our wealth means we are constantly surrounded by foods rich in fats and sugars, UPFs and non-UPFs, which can make avoiding this hedonistic eating a bit of a challenge. Our brain really can be quite capricious; demanding we stop eating while compelling us to eat just one more chip.
The elaborate signalling that occurs to maintain our energy levels and hunger also provides ample opportunity for medical science to intervene when things have gone wrong. The most famous intervention at the moment are the drugs known as GLP-1 receptor agonists, like Ozempic, Trulicity, Byetta and others1. All of these molecules mimic the natural molecule GLP-1 and are agonists of the GLP-1 receptor. If you remember from the coffee and chilli posts, molecules that bind to protein receptors can be agonists or antagonists; agonists stimulate a response from the receptor protein and antagonists prevent a response. All the GLP-1 medications are activating the GLP-1 receptor, that is they are producing a more pronounced GLP-1 effect than the body would be experiencing on it’s own.
As we saw above GLP-1 is released by the brain after signalling by the Vagus nerve shortly after we start eating and it not only contributes to the feeling of satiation but it also slows the rate of gastric emptying2. That is GLP-1 is one of the signalling molecules involved in the movement of food through our gut, specifically it prolongs the amount of time that food will stay in the stomach and so also prolongs the time before we get hungry again after eating.
But, because this is biology, GLP-1, is involved in other feedback loops. It also influences blood sugar levels by increasing insulin secretion from pancreatic beta cells (but only when blood glucose levels are high preventing hypoglycemia) and repressing glucagon secretion. We know that both of these effects also reduce hunger. In fact the influence of GLP-1 on blood sugar levels is why the drug was developed as a treatment for diabetes in the first place. It’s a fortuitous side-effect for dieters, and pharmaceutical companies, that GLP-1 can also be used as a weight loss drug.
The way our body regulates our food consumption and state of hunger is enormously complicated and I’ve only scratched the surface of this topic. In our modern societies we are often trapped between our compulsion to eat and the easy availability of foods that maybe aren’t that great for us when consumed in abundance. Whether understanding why we get hungry is any use in this daily struggle it’s hard to say, but I do like to think that we are not slaves to our chemistry and we are able to exert a level of control, or will, above our homeostatic processes. Whether I’m right about that is probably one for the philosophers.
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