Why don’t others get fat? Nature: Gene mutation, there are people who do not eat fat

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Is there anyone around you who eats without getting fat?

You are obviously a piece of fried chicken, burgers and milk tea drinks. You are “inflated” as if you are blowing air, but she/he is still so thin, I am really envious.

Those of us who are prone to gain weight are prone to feel guilty after eating one more bite. All kinds of delicious food have to be controlled. In order to lose weight, we have suffered enough.

But there are those “children of heaven” in the crowd who don’t get fat no matter what they eat. In the past, everyone said that such people do not exist. They must have exercised a lot, or actually did not eat that much.

But a recent study in Nature suggests that there are children of the Chosen, who are born with genetic mutations and burn energy through a complex set of mechanisms Very fast.

What the hell is going on? Can we replicate this physique too? Losing weight is so much easier.

Nature: Inosine increases energy expenditure

A new paper published in the world’s top academic journal Nature proves that a metabolite called inosine can accelerate fat burning.

→Inosine increases brown fat energy expenditure

What is inosine? It is a nucleoside, mainly found in tRNA, that is important for translating the genetic code during cell division.

Muscle movement requires a series of purine nucleotide reactions, and because inosine is an intermediate, there was a time when athletes used inosine to improve performance, but studies have found that Nothing helps.

Inosine is metabolized to uric acid in the body, which can act as a natural antioxidant and may have neuroprotective effects, but no effect on energy metabolism has been found before.

In experiments with mice, supplementing inosine with a high-energy diet allowed the mice to eat large amounts of food without gaining weight, while avoiding the risk of diabetes.

How inosine works its magic depends on a special type of fat, brown fat.

Brown fat should be familiar to everyone, it is the legendary “good fat”, the undercover in fat. Because not only is it small and won’t make us fat, but it can Accelerates fat burning.

The fat and greasy fat in our impression is white fat, which is widely distributed in the subcutaneous tissue and around the internal organs. It is not for gaining weight, but for storing excess energy.

Brown fat has a large number of mitochondria in the cells, which can convert the energy in food into heat energy, and its role is not to give us weight, but to heat the body.

So, that’s why winter swimming and cold showers can activate brown fat, and brown fat gets the “cold” signal and starts desperately Work.

It has now been found that inosine can also activate surrounding healthy brown fat cells, enhance energy expenditure, and induce “browning” of white adipose tissue to brown fat.

How does inosine increase energy expenditure?

How does inosine enhance brown fat energy expenditure? The process of experimental discovery is also ingenious.

→dying brown fat cells signal

The researchers first induced apoptosis in mice with prolonged thermoneutrality conditions, under which endothelial cells or immune cells did not matter, but brown fat Cells undergo massive apoptosis.

We all know that some metabolites are released during apoptosis, but which metabolites can apoptotic brown adipocytes release?

(Above: Media from thermoneutral dead brown adipocytes applied to healthy brown adipocytes ↑)

An experiment was designed to explore the metabolites released by apoptotic brown adipocytes and their effect on healthy brown adipocytes.

Apply the medium of apoptotic brown adipocytes to healthy brown adipocytes. The purpose of apoptotic brown cells can be known by looking at the response of healthy cells.

The researchers then found that instead of apoptosis, healthy brown fat cells had increased expression of thermogenic genes, which is what we call brown fat activation strong>.

This can be thought of as a “SOS message” from cells that send out “replace me” signals. There are many magical things about our body, and the strong desire of cells protects us all the time.

→Summons extracellular inosine

By combining targeted and untargeted metabolomic approaches, the researchers identified 3 purine metabolites emitted by brown fat: AMP, inosine and hypoxanthine.

The most critical of these is inosine, which approximately doubles the expression of key thermogenic proteins in brown adipocytes and in white adipocytes not less than two orders of magnitude.

(above: the key is the increased expression of thermogenic proteins↑)

That is, dying fat cells release purines to send out a distress signal in order to find rescue, and inosine starts to activate other brown fats as a call for support.

Researchers began to wonder, if healthy cells were stimulated by inosine, would it directly increase energy expenditure?

The results were very encouraging, mice fed a high-energy diet and treated with inosine not only remained leaner, but also protected from diabetes.

How does inosine increase energy expenditure?

If inosine can increase fat burning in brown fat cells, why is it that some people are not fat while others are prone to obesity? That has to do with the mechanism behind this effect.

→What does inosine do?

First of all, we need to clarify, what does inosine do in energy metabolism?

Inosine is an important signaling molecule in cardiovascular physiology, an anti-stress molecule and a regulator of energy use in cells.

Not only that, inosine is required for ATP synthesis and nucleic acid formation; it initiates a cardioprotective response when the body is deprived of oxygen.

This is also why inosine is particularly active under conditions of hypoxia and acute inflammation. because of hypoxia and inflammationDuring the disease, it acts as an endogenous protective mechanism.

Theoretically, we have a lot of inosine in our body, so why do we still gain weight?

This is because the presence of inosine transporter reduces the concentration of extracellular inosine, which naturally cannot promote brown fat burning without extracellular inosine.

→inosine transporter

Inosine transporter, also known as nucleoside transporter 1 (ENT1), as the name suggests, is used to transport inosine. Transport extracellular inosine into cells for use by mitochondria in cells.

Experiments have found that ENT1 deficiency, due to natural or artificial causes, increases extracellular inosine levels, thereby enhancing thermogenic adipocyte differentiation.

For example, there is a drug that actually treats blood clotting disorders, but inhibits the inosine transporter. The researchers gave the drug to mice, which burned more energy.

Humans also have inosine transporters, which are normally active, but due to genetic mutations, 2% to 4% of human inosine transporters Not very active.

That’s why some people don’t get fat by eating anything, they are genetically “lean-prone”.

Can we become lean?

Seeing this, are you also sour? Why am I not one of those 2% to 4%!

Don’t worry, I have a trick to help you become such a lean physique, which is to activate the brown fat in the body as much as possible, and even convert white fat into brown fat.

→Activate brown fat

Brown fat in the body is not supposed to be like this, such as babies and young children, although they are fat, they have a high proportion of brown fat.

Our habitual living environment creates typically thermoneutral conditions, with degradation of brown fat in adults.

The more obvious features are the loss of mitochondrial mass and the accumulation of fat.

Studies show that endogenous fatty acid synthesis is key to brown fat degradation. In turn, endogenous fatty acid synthesis is controlled by carbohydrate response element binding proteins.

In other words, excessive intake of carbs activates the relevant response element binding proteins to form endogenous fatty acids, which ultimately degrade brown fat.

Yes, endogenous fatty acids have nothing to do with our intake of fatty acids, but carbs are dangerous.

Carb intake should be reduced to protect brown fat from degeneration.

Many low-carb dieters find that they are less afraid of cold after a low-carb diet, which may also be related to this.

What can be done to activate brown fat more? I think you’ve already seen it: Cold. Whether it’s winter swimming, cold showers or cold environments, it can effectively increase brown fat.

Also fasting and adding strength training can help increase brown fat.

Key Thin Dragon Says

At the end of the Nature study, the researchers also considered whether it could be used for obesity treatment, such as drugs that interfere with transporter activity.

The drug used in the experiment for blood clotting disorders is one of them, but after allJust a mouse experiment, further research in humans is needed.

Personally, it is a possibility to inhibit the activity of inosine transporter, but it is still uncertain whether it will have other consequences, so this method should wait.

The most feasible way is to protect brown fat as much as possible, and eat less sugar, high-carb snacks, and refined carbohydrates such as rice and noodles.

Also, warm winter conditions contribute to brown fat degradation. In winter, when the heating is turned on more and more, the body will gradually think that the endogenous “stove” is no longer needed.

I know the feeling of being cold is not good. Many people have tried cold showers, but they may not be able to bear it and eventually give up. They have to adapt slowly. Related reading: Can I lose weight by wearing less clothes in winter? How cold does it need to be to activate brown fat?