Leptin: the satiety hormone from fat tissue?

The regulation of body weight is often reduced to a simple equation: energy intake and energy expenditure have to be in balance. If one factor exceeds the other, you gain or lose weight. Put simply: if you eat more calories than you need, you gain weight. If you eat fewer calories than you need, you lose weight.

So far, so good. In practice, unfortunately, it turns out not to be that simple. Once you are carrying a little more around the hips, lasting weight loss becomes a real challenge, even though you “only” have to eat a little less. In truth, when weight fluctuates, either upwards or downwards, the hunger and satiety signals are partly thrown badly off course. The metabolism is in disarray and usually makes it extremely difficult to move the number on the scales back towards “normal”.

Understanding this “chaos” is not easy, because the natural regulation of hunger and satiety is incredibly complex: information from the amount and composition of the last meal, from movement, from the stress level or even from smells and impressions is taken into account. These relatively short-term signals (for example, what and how much have you eaten?) are also extended by long-term information from our fat stores (how much energy have you stored for harder times?). All these different signals are carried to headquarters, the brain, among other routes via nerves and hormones, and are then processed. If you add a bit of genetics and the manipulative power of the food industry to all of this, understanding these processes becomes even harder, and it only hints at why the equation described above is not “perfectly simple” for everyone.

In this article we dive a little into the depths of our metabolism and shine a light on one part of the complicated regulation of satiety: we look at the hormone leptin.

What tasks does it have? How does its effect change when weight is gained or lost? Does it have something to do with failed attempts at losing weight? Does the ketogenic diet influence the hormone?

Look forward to it! But be warned: it gets scientific

Leptin is released by the fat cells, it is what is known as an adipokine. The more fat you carry around with you, the more leptin is produced. This hormone, only discovered in 1994, has the main task of transmitting a satiety signal, stopping food intake and increasing energy expenditure. So it is a natural appetite suppressant which, because of this function, often stands in the spotlight of weight regulation.

Put very simply, the underlying mechanism is the following:

If the fat stores in the body are well filled, they release leptin. This in turn tells the brain that nothing more needs to be eaten, and the feeling of satiety rises. Energy expenditure is also increased, as nothing more needs to be stored and the energy required can be taken from the fat pads. So leptin says, in effect: enough energy stored! Stop eating!

Here the principle behind it is shown schematically:

If, on the other hand, you have only a few fat pads, then only a little leptin is produced and released. No satiety signal is transmitted by leptin, as the body should be refuelled with new energy (food). Energy expenditure is throttled back so that the body does not run the risk of having too little fuel.

Schematically, you can picture it like this:

It should be mentioned about these processes that these are not fast, short-term signals. So not: polish off a muffin, leptin rises and that is why you feel full. Other mechanisms are mainly responsible for that kind of satiety. Leptin is more like a fuel gauge for the fat stores, giving information about long-term reserves.

How important leptin is for the regulation of our metabolism also becomes clear from the following observation: people who cannot produce leptin feel no sense of satiety at all and become very severely overweight in childhood. In these extremely rare cases, giving leptin leads to drastic weight loss and to a normalisation of weight.

Mentioned in passing: there is also a hormone that does exactly the opposite. Ghrelin is, among other things, responsible for making us feel hungry. It is not released from the fat cells, however, but from the stomach and the pancreas.

Back to leptin: what happens there is actually rather clever. So in a certain way leptin protects the body from putting on more fat and thus keeps the fat stores in balance.

So what more could you want?

Once again real life brings us back down to earth, because not everything runs as easily as you would wish.

Since leptin has a satiating effect and can therefore counteract excess weight, it has been investigated in numerous studies for a potential use in weight loss. Put simply: inject leptin, feel fuller in the long term, lose weight. That is the theory. Unfortunately, in practice giving it has not achieved the desired results.

How can that be? Surely leptin should curb hunger?

You would think so, but in people who are overweight leptin is not lacking. On the contrary: it is present in large amounts. This is referred to as hyperleptinaemia. Despite these high amounts of leptin, however, no sufficient satiety signal is achieved. The mechanisms described above are the ideal state in full health and without being over- or underweight. As soon as this state drifts in another direction, the whole thing comes apart.

In the case of excess weight you mostly come across the term leptin resistance, a state in which high amounts of leptin can trigger neither satiety nor weight loss.

The following graphic summarises the state of leptin resistance schematically: when someone is overweight, a lot of leptin is released by the fat cells (the state of hyperleptinaemia). The effect fails to appear, however, no satiety signal is produced and energy expenditure is not increased either. As a result food intake increases further, and the vicious circle is in full swing.

The exact mechanisms behind the absent effect are still not sufficiently understood and clarified today. I know I am repeating myself, but: it is very complicated.

The latest findings support a theory in which all that leptin does indeed reach the brain and also “docks” at the corresponding places. It gives the nerve cells no rest, wanting constantly and at all times to make it clear that enough energy is stored in the body. This information is not translated into a satiety signal, however. At some point that has still not been clarified, the signal does not get through. Somebody is blocking it, no longer feeling like shouting “satiety” all the time. That is why it still cannot be said today what exactly goes wrong in the case of leptin resistance. The latest findings even call the word “resistance” into question, since the leptin apparently arrives at its destination and also passes on the information there. Why it does not get through has not yet been clarified, though.

So unfortunately it is not yet possible to say exactly why all that leptin does not unfold its effect as a satiety maker when someone is overweight and therefore cannot keep the fat stores in balance either.

Research is of course going full steam ahead to clarify all the open questions. In a renowned specialist journal an extremely interesting study on the subject of leptin resistance was published these days (September 2019): instead of the previous approaches of administering even more leptin in order to reduce weight, the research group reduced the amount of leptin in the state of hyperleptinaemia (leptin was, in effect, inactivated, rendered ineffective). As a result the test animals lost weight and their diabetes markers were improved as well. That means that a reduction in leptin leads, at least in the animal model, to the satiety signal getting through again. For the future this approach holds a great deal of potential for achieving successes in the fight against obesity and diabetes in humans too. Super exciting! (9)

After this short excursion into the world of the very latest science, we now turn to fighting the unwanted leptin resistance. From the preceding information we can conclude that the following scenario is desirable: a state in which the body processes the leptin signal and translates it into satiety information. This state is called leptin sensitivity.

At a normal weight this sensitivity mostly works wonderfully. That means that weight loss and a reduction in body fat percentage in the case of excess weight and leptin resistance is the only step for steering the hormonal system back onto a better course. Of course that is not at all easy to manage when hunger and satiety signals are not working properly, especially as a great deal often has to happen on the scales before the hormonal system has settled down again.

The example of leptin shows that “just take in fewer calories than you need, then losing weight will work too” can become a mammoth task. Because in cases of severe excess weight hunger and satiety often do not work the way they actually should, and they make it harder for the kilos to drop off. (Of course many other factors besides leptin also play a role here.)

Once the metabolism is in disarray, an attempt has to be made to get it back onto natural tracks. Processed foods do not help with that, because they are designed by the industry for exactly the opposite: to increase (cravings for) hunger and desires, so that you buy and eat even more of them. Anyone who has ever tried to reduce calories by eating a little less, but still has ready meals and the like on the menu every day, knows what is meant. Successes do not last, because sooner or later the cravings strike again.

The way out? Healthy and fresh meals which address the feeling of hunger and satiety in the right way and which normalise body weight through an adapted reduction in calories. In addition, enough exercise to fire up energy expenditure, and you are on the right path. Of course that is hard, very hard even. But not impossible. And only in this way can you reach your goal permanently and get your metabolism moving again. It is the best possibility (if not currently the only one) of escaping the vicious circle. The fat stores are reduced, the leptin signal (among others) becomes effective again and the natural feeling of hunger and satiety can get back onto the right track. Crash diets? With extremely low amounts of calories they only throw the body into even more disarray and do not help you reach the goal in the long term.

We have now talked a lot about the fact that too much leptin can no longer unfold its effect. But what is it actually like when only a little leptin is buzzing around in the body?

Little body fat means that only a little leptin is produced. As a result appetite rises and energy turnover falls. Ha! A falling energy turnover? That is pretty annoying, isn’t it? After all, it means that less energy is needed to keep our body running? Correct. Through this mechanism the body protects itself. Little fat means that only a little energy is stored. If food now becomes scarce, you really do get problems. So better to throttle the engine back and be sparing with what you still have.

You reach this state, for example, through severe underweight. The consequences are usually strong cravings (leptin provides satiety, remember?) and a reduced energy turnover. In addition, fertility falls, among other things, and stress levels rise.

At this point it must of course also be said that the scenario described is not determined exclusively by leptin. Other factors have a hand in it too. Perhaps I have said this once already: a complex business, this metabolism.

The ketogenic diet, which is characterised by very low amounts of carbohydrates alongside increased amounts of fat, leads in most cases of severe excess weight to very good success in losing weight. In addition, increased satiety is reported compared with other forms of nutrition. But how do things stand with leptin here? Does it have something to do with satiety in this case?

Although leptin levels drop sharply on a strongly carbohydrate-reduced diet, leptin sensitivity does appear to be improved. The already demonstrated anti-inflammatory effect of this form of nutrition is discussed as the cause, because: leptin resistance appears to go hand in hand with inflammation in the brain. (4) If this is counteracted, the effect of leptin could improve in this way too. (2) (5)

So this form of carbohydrate-reduced nutrition does appear to be able to increase the natural feeling of satiety. In addition to the hormonal cause for this (increased leptin sensitivity), the direct influence of the ketones on the brain, as well as connections with the gut microbiota, are presumably further factors not to be dismissed.

In all probability it is the combination of everything, which makes the ketogenic diet not only a successful tool for short-term weight loss, but also for long-term weight control. (7)

Before the end of the article, a small comment still has to be added: the appetite brake leptin also has a direct and indirect influence on a large number of further processes in the body (not only on hunger and satiety). Leptin levels are connected, among other things, with thyroid hormones, sex hormones and cortisol levels. The example of underweight, in which fertility decreases among other things, already hints at the waves a small hormone can make.

We will devote ourselves to these processes another time, though.