Hormones from adipose tissue

Adipose tissue? That is there for storage. It stores fat. This is what most people know about adipose tissue. But did you know that your adipose tissue can do a great deal more? It releases hormones all day long. With this ability it is the largest hormonally active organ in our body.

First of all we need to clarify what „adipose tissue“ actually is. There is white and brown adipose tissue. White adipose tissue serves to store triglycerides, in other words fats. Brown adipose tissue stores less fat, but in return it can heat our body up like a hot water bottle, the keyword being „thermogenesis“, and that is something for another time. Today we are talking about white adipose tissue, the storage fat tissue. This tissue consists of white fat cells (adipocytes). Like every other cell, they have a nucleus, mitochondria and all the other building blocks of human (animal) cells. Their main feature is a large vacuole. This is a storage station for the fat. A big fat droplet of fat containing triglycerides. That means that the whole cell is not filled with fat, only this vacuole. So in the other parts of the cell, cell division and other important things can be worked on undisturbed. The vacuole takes up most of the space in the cell, and all the other cell components are squeezed flat against the cell membrane as a result. Being a nucleus in an adipocyte is probably not the most comfortable position. But then again, somebody has to do that job too.

White adipose tissue is well supplied with the finest little vessels (blood capillaries) in order to ensure that the cells are nourished and to allow the storage fats to be transported in and out. Besides fat cells, fibroblasts (connective tissue cells), monocytes and macrophages (cells of the immune system) are also bustling about in adipose tissue.

„… and why do we have adipose tissue at all?“, you might think, „it is a pretty annoying, unsightly thing.“ Nope! Let us turn the perspective around and think the whole thing through from the point of view of evolution. A few people are sitting around the campfire grilling a wild boar. Everyone eats one portion, chews every bite 30 times, drinks a glass of water with every bite, says „I am full“ and they leave the rest of the wild boar lying there so that no feeling of fullness comes up. The remains of the boar are dragged away by other animals. The next day our little band of people gets hungry again, but oh dear, Mother Nature does not send them a wild boar today. The hunger grows, they feel weak, they get tired and they fall asleep. Forever. Can we agree that we will not get far with this system? Good. So these people need something they can store energy with while there is something to eat available. Lucky that adipose tissue exists. So our people are sitting around the campfire, they do not give a damn about chewing and they really stuff themselves with wild boar. After all, they do not know when they will next find one. So in it all goes. In the end they are stuffed and fall asleep happily. Part of the wild boar energy they burn off again straight away. Everything they do not currently need is converted into fat and stored in the adipose tissue. The next day they do not catch a wild boar. But that is not a problem, because their body switches over to fat burning and ketosis and their muscles and brains are supplied with energy from the adipose tissue. When the stores begin to run low, the hunger grows and with it the urge to find something to eat again. You can read up on exactly what happens in our body in our article “What happens in the metabolism without carbohydrates?“.

What if the wild boars came past voluntarily every day? Would our little band then tuck in day after day and would their fat stores get fuller and fuller? Hardly. Because deep inside, their biochemistry knows that the day may come when no more wild boars dance past as if in a land of plenty. Then it is time to hunt…. and with 200 kg on the scales and fat stores wobbling about, hunting somehow does not go all that well.

That is why evolution has built plenty of regulatory mechanisms into our bodies. So that we fill up our stores at the right time and stop doing so again at the right time, in order to stay people who can move. The most important regulatory mechanism is controlled by a hormone from the adipose tissue: leptin. All the other hormones and substances that adipose tissue releases serve above all for regulation too: should new fat cells be formed at the moment? Should hunger rise? Should the person up there move about less?

A small side note: yes, through „modern food“ we have successfully managed to override many of these regulatory mechanisms. Congratulations, food industry! That is why another task of good nutrition is to bring hormonal regulation back into its natural channels.

The best known hormone released by adipocytes is leptin. It is encoded by the „obese“ gene. More than 60 years ago a laboratory mouse was discovered, more or less by chance, that simply kept getting fatter and fatter. While its fellow mice stopped eating after an appropriate intake of food, the „ob/ob“ mouse just kept on eating and eating. The reason was a genetic defect: this mouse was missing the „obese“ gene, which contains the information for leptin, which is why it is called the ob/ob mouse (the gene was missing on the chromosome from the mother as well as on the chromosome from the father, so the anomaly was homozygous. The gene defect is inherited recessively). Although mice with this gene defect had been known for a long time, the hormone leptin was not discovered until 1994.

Leptin is released by white fat cells and binds to receptors in the brain. There it provides information about how large the fat stores currently are. If the fat stores fall, less leptin is produced. If the amount of reserves rises, more leptin is released. In the brain, leptin blocks the release of two appetite stimulating substances (AgRP = agouti related protein and NPY = neuropeptide Y). Fewer appetite stimulating substances means less appetite. At the same time, leptin stimulates the release of two appetite suppressing substances in the brain (POMC = proopiomelanocortin and CART = cocaine and amphetamine regulated transcript). So through this, leptin has an effect on satiety, and that makes sense: the more reserves we have, the less we need to top up. When the fat reserves begin to run low, the leptin concentration falls and the effect is reversed: hunger rises.

At the same time leptin also stimulates the sympathetic nervous system and thus leads to blood pressure rising, heart rate rising and brown adipose tissue carrying out more thermogenesis. Energy expenditure goes up.

In the opposite case, energy expenditure falls. Ah, there it is: the dreaded drop in basal metabolic rate. But it can all be brought back under control with the right (and sufficient) nutrition.

Now you might think: „Easy peasy, surely we can produce leptin in a test tube and just like that we have THE perfect means of suppressing appetite and losing weight“. Yes, one or two people have already had that idea and have injected leptin into people who were overweight. And what happened? Nothing at all.

People who are severely overweight have plenty of adipose tissue. Plenty of adipose tissue means plenty of white fat cells producing plenty of leptin. Plenty of leptin in the bloodstream, plenty of leptin in the brain… and they still put on weight? Why? At some point the regulation failed and the balance between energy intake and energy expenditure was disturbed. Two possible reasons are emotional eating and eating the wrong things. From childhood on we are taught that eating is more than just a means of stilling hunger, so we simply ignore our satiety. At the same time the food industry does everything it can to bring ever more addictive products onto the market. The right ratio of sugar and fat is very good at overriding our natural satiety mechanisms. 50:50 is one such devilish ratio. 50 % carbohydrates, 50 % fat…. chocolate (sugar plus cocoa butter), crisps (potatoes plus oil), ice cream (sugar and cream)….

So we ignore the satiety effect, or it is circumvented with combinations like these. We put on weight, more and more of it, and at some point natural hunger no longer makes itself felt at all, all the floodgates are open and we could eat all day long. Why?

Leptin. Leptin, or more precisely a malfunction of leptin signal transmission, is the underlying control mechanism when we can eat and eat, no matter how much it was and no matter how full our reserves already are. Because, as described above, the leptin level keeps rising as the reserves rise. We could stop eating now because we are getting full, but we do not. We go on eating despite satiety because we want to reward ourselves, because we are sad, or because the food is „addictive“. Then at some point the point is reached at which there are masses of leptin in the body. The brain continuously gets the message „Hello brain, this is the adipose tissue speaking, my cells are sufficiently full“. The brain switches to „full“ but nothing happens. More fat comes into the adipose tissue, the cells are filled to bursting and the adipose tissue reports „Hello brain. This is your fat. That is slowly getting to be enough“. The brain switches to „full“ but we go on eating. So that the fat cells do not burst, the adipose tissue expands, new fat cells are formed. „HELLO BRAIN! This is your adipose tissue speaking!!! We are really running out of room down here! It would be very nice if you would finally tell your human to stop stuffing himself!“. The brain tells the human „we are full“. Human goes on eating, it tastes so good after all and grandma cooked it. „HEY BRAIN! IF YOU DO NOT MAKE SURE IT GOES QUIET DOWN HERE SOON, MATE!“. The brain shoots back „Hey fat, now listen. I have been telling this human the whole time that he is full, what else am I supposed to do, tie his mouth shut? Great, and on top of that I get shouted at by you. You keep turning up here with your leptin comrades. You know what? That is enough! You can both get lost. You, adipose tissue, talk to the hand, the head is not listening to you. And you, human: your own fault… then just keep stuffing yourself. I have had it. You two are welcome to sort this out, but without me“. Bang. Crash. Leptin resistance.

Now the adipose tissue can release as much leptin as it likes. The information no longer arrives in the brain. And it is no use injecting leptin into the crook of the arm of this overweight person either. The information no longer gets through. The brain is deaf, it has had a sudden hearing loss where leptin is concerned and simply has no strength left to take the message in. The satiety mechanism has been overridden. And even though the fat stores are filled to bursting… you are hungry and hungry.

This leptin resistance can only be reversed by the fat reserves shrinking. Losing weight, down to a normal weight. Because only when the leptin shouting dies down can you get the brain to listen again. After all, you can hardly listen to the birds twittering when the pneumatic drill is breaking up the asphalt next to you. But as soon as the pneumatic drill stops making a racket, your ears only need to calm down a little and you can hear the birds again. Leptin resistance is like that too, and fortunately it is reversible.

Right, but now something completely different. Away from being overweight: leptin leads to regulation with underweight as well. If you lose a lot of weight or do the wrong (crash) diet, the leptin level falls and that leads to cravings, so that the reserves are filled up again. If the person does not follow this hunger but goes on losing weight (down into underweight), the falling leptin level leads to less energy being used: body temperature falls, you feel cold, hair growth slows down and reproductive capability is shut down (periods stop). So leptin has an immense effect on our body. This hormone from the adipose tissue has an influence on almost every bodily function.

By the way: with a diet that is too low in calories or a strong restriction of carbohydrates, the leptin level falls faster than the fat reserves. The information „there is an emergency here“ reaches the brain before there is any real emergency at all. That is why I never recommend going below 1600 (healthy paleo) calories, and only for very inactive and petite people can 1400 sometimes be the minimum. In addition, if you are following a reduced carbohydrate diet, you have to listen to your body. I recommend a ketogenic diet for 30 days up to 3 months at a stretch, until all the adaptations have taken place. After that, though, you should do a refeed once a week, as a woman possibly even twice a week (on one evening in the week eat 150 to 300 g of carbohydrates from rice, potatoes, sweet potatoes or pumpkin), so that leptin release is stimulated again. That way you can also keep a ketogenic diet going healthily in the long term. If you are coming from a higher weight, even 6 to 12 months at a stretch can be perfectly fine, but here I always like to look at each person individually and only then decide how long a ketogenic diet is suitable at a stretch, and when the body needs another leptin boost from carbohydrates.

Adipose tissue releases what are called „adipokines“. That is the name for the hormones and substances that are released from adipose tissue). Besides leptin, other hormones are adiponectin, resistin, visfatin and hepcidin. They influence and regulate glucose metabolism, fat metabolism and the feeling of hunger.

Further substances are inflammatory factors, clotting factors and also the transcription factor TNFα (TNF alpha = tumour necrosis factor alpha). These cytokines mainly regulate the differentiation of stem cells into further adipose tissue cells, but they are also connected with inflammatory diseases, type II diabetes and clotting disorders.

It should be a concern for all of us to keep our fat reserves within a natural range. Not too much and not too little.

Good luck with that!
Cheers, Marina