What determines your desire for wine

At the end of September 2020, the world-famous folklore beer festival, the Oktoberfest, will be held in Munich, Germany. Rasmussen, a journalist from Denmark, went to the local editor to write an article about the physiological changes caused by booze. He stayed at the Oktoberfest for 3 days and drank 7.5 liters of beer on average every day. Despite getting drunk every day, Rasmussen did not forget the purpose of this trip. He invited Knopp, a metabolic physiologist at the University of Copenhagen, to get some professional advice.

The Knopp team originally planned to conduct a study: What is it that determines a person’s desire to drink? However, considering that large amounts of alcohol may cause serious health problems for volunteers, the plan was shelved. And now, Rasmussen, who took the initiative to come to the door, is of course a volunteer, and Knopp readily agreed to his invitation.

Alcohol consumption is related to FGF21
In life, people drink alcohol for a variety of reasons. It may be to taste the deliciousness of the wine itself, it may be to relieve stress, to seek excitement or to socialize, or it may not be for any reason at all. What is certain is that drinking behavior is greatly influenced by genetics. However, the latest genomic research results show that the genetic mechanisms of normal social drinking (such as Rasmussen’s binge drinking at the Oktoberfest) and abnormal drinking (such as alcohol abuse) seem to be completely different, and the mechanism behind the latter behavior is very different. complex. When the physical condition is not suitable, even normal drinking behavior may have adverse effects on health. Therefore, Knopp wanted to find out which genes and mechanisms determine a person’s desire to drink.

Around 2005, fibroblast growth factor 21 (“FGF21″), a hormone secreted by the liver, received attention for the first time in an experiment for causing weight loss in mice. Since then, more and more studies have found that FGF21 has important physiological effects, such as influencing people’s food choices: whether to eat carbohydrates or protein? Why do some people prefer sweets?

The Knopp team focused on FGF21. Three days later, they tested Rasmussen’s blood samples. As expected, the FGF21 levels in the blood samples soared. Even a few days after Rasmussen returned to Denmark, his FGF21 levels were still twice as high as normal. Prove that there is indeed a connection between alcohol consumption and FGF21.

FGF21 reduces drinking pleasure
In 2016, a large genetic study carried out in 100,000 European volunteers found that there were 2 gene variants of beta-closin (an enzyme that helps to receive FGF21 signals) and non-addictive drinking desire Related: People who carry the first variant are light drinkers or non-drinking, while those who carry the second variant enjoy the joy of booze.

Based on the results of this study, Knopp’s team conducted experiments with mice and monkeys. After injecting them with FGF21, their desire for sugar water intake was greatly reduced. They continued to experiment and replaced sugar water with a simple sugar derivative—ethanol (alcohol). As a result, the two animals’ desire for ethanol intake was greatly reduced. Later, they discovered that FGF21 did not directly reduce the desire for sugar or ethanol in mice or monkeys by affecting the taste of mice or monkeys, but by activating the hypothalamus (the operating area of ​​the brain’s reward mechanism), thereby reducing the intake of sugar or sugar. The pleasure of ethanol.

Next, the Knopp team destroyed the beta-closin in the mice, and the mice really started to consume more ethanol. Knopp conjectured that since mice lacking beta-cloxin tend to consume more ethanol because of more pleasure from ethanol, is this the same for humans?

Why are people sensitive to FGF21?
Previously, some hormones have been proven to slightly reduce appetite by affecting the brain’s reward system. Why can FGF21 significantly reduce people’s desire to drink? A reasonable explanation is that human ancestors ate a lot of fruits (including fermented fruits) and thus consumed a lot of fructose and ethanol. The metabolic process of fructose and ethanol will bring a great burden to the liver, which is also the reason why excessive drinking can damage the liver. From another perspective, FGF21 transmits the signal from the liver to stop drinking to the hypothalamus, which is equivalent to the liver saying to the brain: “We already have enough fructose and ethanol! Can you take a break? Clean up fructose and ethanol?”

Knopp speculated that the reason why the human body has such a strong feedback on FGF21 is probably because we have mastered the method of winemaking, and the alcohol content in wine is relatively high. After all, the ethanol consumed by direct drinking is far more than the ethanol produced by the natural fermentation of fruits. Therefore, our body has evolved a set of mechanisms to control the desire to drink in order to avoid alcohol poisoning, that is, the “liver-FGF21-hypothalamus” mechanism. Although this is only speculation, FGF21 does protect the liver to a certain extent. However, the current research only confirms that FGF21 has the effect of reducing the desire to drink in the short term, and whether it can have a long-term effect is still unknown.

FGF21 treats excessive alcohol consumption?
The research results of Knopp et al. not only reveal what happens to the human body after heavy drinking, but also propose a new idea to help people quit drinking. Just as the pancreas of patients with type 2 diabetes is overwhelmed and difficult to produce insulin, the liver that has been exposed to high concentrations of ethanol for a long time may also lose its ability to secrete FGF21. The aforementioned Rasmussen has a high level of FGF21 in blood samples after drinking a lot of alcohol. It is precisely because he is not a real “alcoholic” that his liver can secrete enough FGF21.

Vervet monkey who loves to steal alcohol.

An in-depth study of the FGF21 secretion of problem drinkers may help determine whether injecting an appropriate dose of FGF21 can help them reduce their desire to drink. To test this idea, the Knopp team changed the test subject to an animal that is notorious for stealing alcohol and drinking—the vervet monkey. Because the drinking tendency of vervet monkeys is very similar to that of humans, they selected some “drunkard” vervet monkeys to experiment. Give them 3 bottles of red wine every day at the beginning, and then give them FGF21 injections a few days later. As a result, the daily alcohol consumption of these vervet monkeys has indeed fallen. This seems to indicate that FGF21 can solve the problem of alcoholism and even repair liver damage. However, to explain how much alcohol a person has, FGF21 alone is not enough. In addition. Because drugs that can interact with the brain’s reward system have the risk of causing depression and other mental problems, there is still a long way to go before FGF21 can be used as a drug to treat problem drinking.

Regardless of whether the FGF21 therapy is successfully developed, we already know that the liver is like a thinking organ that controls our desire to drink in a unique way. When we drink more and more, the liver releases the hormone FGF21, so that the pleasure we get from alcohol gradually disappears. Therefore, if your wine no longer makes you happy, then it’s time to put down the wine glass.

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