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Why are people hungry? This is an issue that has always been of great concern to everyone.
Although we always say "hungry" or "full stomach", in fact, the gastrointestinal tract is controlled by autonomic nerves.
Whether it is empty or not and whether it needs to eat is actually not perceived by the self.
Humans feel hungry.
The reason may still be in our brains.
Science reveals the secret of the hunger switch in the brain.
On April 15th, researchers from the Weizmann Institute of Science and the research team from Queen Mary University of London and the Hebrew University of Jerusalem jointly revealed the master switch for hunger-melanocortin receptor The activation mechanism of body 4 (MC4 receptor).
When the receptor is activated, people feel full, and when the receptor is inactivated, people feel hungry.
In addition, they also clarified how the drug setmelanotide (Imcivree), which is used to treat obesity, activates the switch.
These findings provide new insights into ways to control hunger and may help develop improved anti-obesity drugs.
The research results were published in "Science" (Science).
Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling.
DOI: 10.
1126/science.
abf7958 The MC4 receptor is present in a brain region called the hypothalamus-a cluster of neurons, which processes various energy-related Metabolic signals are used to calculate the energy balance of the human body.
When MC4 is activated or "turned on" (usually on), it will issue commands to make us feel full, which means that from the perspective of the brain, our default state is fullness.
When our energy levels drop, the hypothalamic cluster produces the "feeding time" hormone, which inactivates or shuts down the MC4 receptors, signaling "become hungry".
After eating, the second "I'm full" hormone is released.
It binds to the same active site on MC4, replacing hunger hormone and reopening the receptor-bringing us back to the default value of satiety.
Mutations that inactivate the MC4 receptor can keep people hungry.
MC4 is the main target of anti-obesity drugs such as setmelanotide, but until now, it is unknown how this hunger switch works.
This new study originated from a special family: in this family, at least 8 members are severely obese due to constant hunger.
Most of them have a body mass index (BMI) over 70, which is 3 times that of the average person! The researchers unexpectedly discovered that the cause of severe obesity in these family members was due to a single mutation in the family: a mutation that affected the MC4 receptor.
Then she turned to Dr.
Moran Shalev-Benami from the Weizmann Department of Chemistry and Structural Biology to ask whether the new advances in electron microscopy could help explain how this particular mutation can have such a devastating effect.
Shalev-Benami decided to study the structure of MC4 and invited Israel to join her laboratory as a guest scientist.
Israel and Dr.
Oksana Degtjarik, a postdoctoral researcher in the laboratory, isolated a large number of pure MC4 receptors from the cell membrane, combined it with setmelanotide, and determined its 3D structure using cryo-electron microscopy.
The 3D structure shows that setmelanotide activates the MC4 receptor by entering its binding pocket-directly triggering the molecular switch for satiety, and is even more effective than natural satiety hormone.
Facts have proved that the drug has a surprising auxiliary effect: calcium ions enter the binding pocket to enhance the binding of the drug to the receptor.
In biochemical and computational experiments, scientists found that, similar to drugs, calcium helps satiety hormone to activate MC4 receptors, while interfering with hunger hormone and reducing its activity.
Obviously, the satiety signal can successfully compete with the hunger signal because it benefits from the help of calcium, which helps the brain to restore satiety after eating.
The structure of MC4 also shows that the entry of drugs will cause structural changes in the receptor.
These changes seem to trigger signals in neurons, which can lead to feelings of fullness.
This study explains how mutations in the MC4 receptor interfere with this signaling, leading to endless hunger and ultimately obesity.
In addition, scientists have discovered the difference between MC4 and similar receptors in the same family from the structure of MC4.
Based on this result, drugs that only bind to MC4 can be designed in the future to avoid possible side effects caused by interaction with other receptors.
The findings of this study can help develop better and safer anti-obesity drugs that will target MC4R more precisely.
Nature Sub-Journal: Why are some people more hungry? Coincidentally, on April 12, a study in Nature Metabolism, a journal of Nature, also explored why some people are always more hungry than others? The results of the study show that blood sugar may be causing trouble! A few hours after eating, people who have a sharp drop in their blood sugar levels will end up feeling more hungry than others.
clevelandclinic The research was jointly carried out by experts from multiple countries including King's College London, University of Leeds, Harvard Medical School, Massachusetts General Hospital, etc.
The research results come from PREDICT, the world's largest ongoing nutrition research program, focusing on reality.
The reaction to food in the living environment, looking for reasons why it is difficult to lose weight even in a calorie-controlled diet, and the importance of understanding personal metabolism in terms of diet and health. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals.
Nat Metab (2021).
doi.
org/10.
1038/s42255-021-00383-x The research team collected 1,070 people who ate standardized breakfast and free choice meals within two weeks Detailed data on blood glucose response and other health markers after eating, a total of more than 8,000 breakfasts and more than 70,000 meals.
Standard breakfasts are mainly muffins.
Under the premise of controlling the same calories, the composition of carbohydrates, protein, fat and fiber is different.
Participants wore a patch continuous blood glucose monitor (CGM) to measure their blood glucose levels throughout the study, and a wearable device to monitor activity and sleep.
Record the exact time of hunger through the collection app.
In addition, participants also underwent a fasting blood glucose response test (oral glucose tolerance test) to measure their body's handling of sugar.
After comparing the participants' conditions when they ate the same test meal, the researchers found that the blood glucose responses of the participants were quite different.
Previous studies on blood glucose after eating have focused on how the level rises and falls within the first two hours after a meal, the so-called peak blood sugar.
However, after analyzing the data, the PREDICT team noticed that some people experienced a significant "sugar dip" within 2-4 hours after this initial peak, and their blood glucose levels quickly dropped below baseline before they recovered.
Compared with the participants with stable blood sugar, even if they ate the same last meal, the hunger of those whose blood sugar dropped rapidly increased by 9%, and the time to eat the next meal was about half an hour earlier.
At the same time, such participants tended to consume 75 calories more in the 3-4 hours after breakfast, and about 312 more calories throughout the day.
This dietary pattern may even cause a weight gain of 20 pounds (approximately 9 kg) in a year.
! In fact, people have always suspected that blood sugar levels play an important role in controlling hunger, but the results of various previous studies are uncertain.
And now the results of the study clearly show that compared with the initial peak blood glucose response after eating, the drop in sugar is more predictive of hunger and subsequent calorie intake, which also changes our perception of blood sugar levels and foods eaten.
Thinking about the relationship.
Kim Spector, professor of genetic epidemiology at King’s College London and the scientific co-founder of ZOE, concluded: "Food is complex, and humans are also complex, but our research has finally opened the black box between diet and health.
We are very happy to be able to bring this together.
A cutting-edge science is translated into home nutrition and microbiome testing, giving everyone the opportunity to discover their unique response to food to best support their metabolism and gut health.
"So, next time you feel hungry easily, When you often want to eat, don't blame yourself for not having enough willpower.
It may be because your blood sugar level drops faster.
Author: Jessica/Oranhgy/Sunny Editor: Jessica authorized to reprint, submit and break the news, please contact Metz Medical Administrator MedSci (WeChat ID: medsci_m)
Although we always say "hungry" or "full stomach", in fact, the gastrointestinal tract is controlled by autonomic nerves.
Whether it is empty or not and whether it needs to eat is actually not perceived by the self.
Humans feel hungry.
The reason may still be in our brains.
Science reveals the secret of the hunger switch in the brain.
On April 15th, researchers from the Weizmann Institute of Science and the research team from Queen Mary University of London and the Hebrew University of Jerusalem jointly revealed the master switch for hunger-melanocortin receptor The activation mechanism of body 4 (MC4 receptor).
When the receptor is activated, people feel full, and when the receptor is inactivated, people feel hungry.
In addition, they also clarified how the drug setmelanotide (Imcivree), which is used to treat obesity, activates the switch.
These findings provide new insights into ways to control hunger and may help develop improved anti-obesity drugs.
The research results were published in "Science" (Science).
Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling.
DOI: 10.
1126/science.
abf7958 The MC4 receptor is present in a brain region called the hypothalamus-a cluster of neurons, which processes various energy-related Metabolic signals are used to calculate the energy balance of the human body.
When MC4 is activated or "turned on" (usually on), it will issue commands to make us feel full, which means that from the perspective of the brain, our default state is fullness.
When our energy levels drop, the hypothalamic cluster produces the "feeding time" hormone, which inactivates or shuts down the MC4 receptors, signaling "become hungry".
After eating, the second "I'm full" hormone is released.
It binds to the same active site on MC4, replacing hunger hormone and reopening the receptor-bringing us back to the default value of satiety.
Mutations that inactivate the MC4 receptor can keep people hungry.
MC4 is the main target of anti-obesity drugs such as setmelanotide, but until now, it is unknown how this hunger switch works.
This new study originated from a special family: in this family, at least 8 members are severely obese due to constant hunger.
Most of them have a body mass index (BMI) over 70, which is 3 times that of the average person! The researchers unexpectedly discovered that the cause of severe obesity in these family members was due to a single mutation in the family: a mutation that affected the MC4 receptor.
Then she turned to Dr.
Moran Shalev-Benami from the Weizmann Department of Chemistry and Structural Biology to ask whether the new advances in electron microscopy could help explain how this particular mutation can have such a devastating effect.
Shalev-Benami decided to study the structure of MC4 and invited Israel to join her laboratory as a guest scientist.
Israel and Dr.
Oksana Degtjarik, a postdoctoral researcher in the laboratory, isolated a large number of pure MC4 receptors from the cell membrane, combined it with setmelanotide, and determined its 3D structure using cryo-electron microscopy.
The 3D structure shows that setmelanotide activates the MC4 receptor by entering its binding pocket-directly triggering the molecular switch for satiety, and is even more effective than natural satiety hormone.
Facts have proved that the drug has a surprising auxiliary effect: calcium ions enter the binding pocket to enhance the binding of the drug to the receptor.
In biochemical and computational experiments, scientists found that, similar to drugs, calcium helps satiety hormone to activate MC4 receptors, while interfering with hunger hormone and reducing its activity.
Obviously, the satiety signal can successfully compete with the hunger signal because it benefits from the help of calcium, which helps the brain to restore satiety after eating.
The structure of MC4 also shows that the entry of drugs will cause structural changes in the receptor.
These changes seem to trigger signals in neurons, which can lead to feelings of fullness.
This study explains how mutations in the MC4 receptor interfere with this signaling, leading to endless hunger and ultimately obesity.
In addition, scientists have discovered the difference between MC4 and similar receptors in the same family from the structure of MC4.
Based on this result, drugs that only bind to MC4 can be designed in the future to avoid possible side effects caused by interaction with other receptors.
The findings of this study can help develop better and safer anti-obesity drugs that will target MC4R more precisely.
Nature Sub-Journal: Why are some people more hungry? Coincidentally, on April 12, a study in Nature Metabolism, a journal of Nature, also explored why some people are always more hungry than others? The results of the study show that blood sugar may be causing trouble! A few hours after eating, people who have a sharp drop in their blood sugar levels will end up feeling more hungry than others.
clevelandclinic The research was jointly carried out by experts from multiple countries including King's College London, University of Leeds, Harvard Medical School, Massachusetts General Hospital, etc.
The research results come from PREDICT, the world's largest ongoing nutrition research program, focusing on reality.
The reaction to food in the living environment, looking for reasons why it is difficult to lose weight even in a calorie-controlled diet, and the importance of understanding personal metabolism in terms of diet and health. Postprandial glycaemic dips predict appetite and energy intake in healthy individuals.
Nat Metab (2021).
doi.
org/10.
1038/s42255-021-00383-x The research team collected 1,070 people who ate standardized breakfast and free choice meals within two weeks Detailed data on blood glucose response and other health markers after eating, a total of more than 8,000 breakfasts and more than 70,000 meals.
Standard breakfasts are mainly muffins.
Under the premise of controlling the same calories, the composition of carbohydrates, protein, fat and fiber is different.
Participants wore a patch continuous blood glucose monitor (CGM) to measure their blood glucose levels throughout the study, and a wearable device to monitor activity and sleep.
Record the exact time of hunger through the collection app.
In addition, participants also underwent a fasting blood glucose response test (oral glucose tolerance test) to measure their body's handling of sugar.
After comparing the participants' conditions when they ate the same test meal, the researchers found that the blood glucose responses of the participants were quite different.
Previous studies on blood glucose after eating have focused on how the level rises and falls within the first two hours after a meal, the so-called peak blood sugar.
However, after analyzing the data, the PREDICT team noticed that some people experienced a significant "sugar dip" within 2-4 hours after this initial peak, and their blood glucose levels quickly dropped below baseline before they recovered.
Compared with the participants with stable blood sugar, even if they ate the same last meal, the hunger of those whose blood sugar dropped rapidly increased by 9%, and the time to eat the next meal was about half an hour earlier.
At the same time, such participants tended to consume 75 calories more in the 3-4 hours after breakfast, and about 312 more calories throughout the day.
This dietary pattern may even cause a weight gain of 20 pounds (approximately 9 kg) in a year.
! In fact, people have always suspected that blood sugar levels play an important role in controlling hunger, but the results of various previous studies are uncertain.
And now the results of the study clearly show that compared with the initial peak blood glucose response after eating, the drop in sugar is more predictive of hunger and subsequent calorie intake, which also changes our perception of blood sugar levels and foods eaten.
Thinking about the relationship.
Kim Spector, professor of genetic epidemiology at King’s College London and the scientific co-founder of ZOE, concluded: "Food is complex, and humans are also complex, but our research has finally opened the black box between diet and health.
We are very happy to be able to bring this together.
A cutting-edge science is translated into home nutrition and microbiome testing, giving everyone the opportunity to discover their unique response to food to best support their metabolism and gut health.
"So, next time you feel hungry easily, When you often want to eat, don't blame yourself for not having enough willpower.
It may be because your blood sugar level drops faster.
Author: Jessica/Oranhgy/Sunny Editor: Jessica authorized to reprint, submit and break the news, please contact Metz Medical Administrator MedSci (WeChat ID: medsci_m)
