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Obesity is one of the top ten chronic diseases identified by the World Health Organization.
Nearly 40% of people in the world are overweight and 13% are obese
.
Obese people are more likely to suffer from diabetes, cardiovascular disease and chronic kidney disease
FTO gene, obesity gene, means that the protein encoded by the gene is a component of a pathway that regulates appetite and energy balance, and the imbalance of this pathway directly or indirectly leads to the accumulation of body fat and weight gain
.
The strongest genetic association with obesity is a set of genetic variants in a gene called FTO
.
More than 40% of people have one copy of these variants, and 16% have two copies, which directly increases the risk of obesity by 70%
On June 4, 2021, researchers from the University of Chicago published a research paper entitled "Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5" in the top international journal Science, which describes a set of genetic mutations.
Affect the expression of obesity-related genes in the brain and adipose tissue
Studies have found that changing the expression of obesity-related genes can produce behavioral changes
.
Mice lacking one of the genes reduced their interest in sweets
The researchers first discovered that the genetic variation in the FTO gene physically interacted with the other two genes IRX3 and IRX5, indicating that these two genes may be related to obesity
.
Then, the researchers designed to knock out the IRX3 and IRX5 genes in mice and found that these mice were thinner, which proved that they are indeed related to obesity
.
Earlier, some scientists thought that FTO mutations may affect fat tissue or hypothalamus, so the research team wanted to know if it would be through the two genes IRX3 and IRX5
.
The researchers used a mouse model that lacked obesity-related regions in the FTO gene to observe the expression of IRX3 and IRX5 genes in different tissues of mice
.
The researchers found that the expression of IRX3 and IRX5 in adipose tissue and hypothalamus were reduced
.
Interestingly, this change in expression level only occurs during embryonic development, but not in adult tissues
To understand the role of these genes in the hypothalamus, the researchers used IRX3 knockout mice and investigated whether these mice had different eating behaviors
.
The researchers were surprised to find that mice lacking LRX3 had less interest in sweets
.
So, is this gene the same in humans? Researchers used data from the genetic testing service "23 and Me" and found that obesity-related FTO variants are also a powerful predictor of human sweet food preferences
.
This indicates that in addition to controlling metabolism, this gene also affects behavioral functions
The researchers showed that the FTO genome region actually contains multiple independent variants, which are all inherited together, and they each affect the expression of IRX3 and IRX5 in adipose tissue and hypothalamus, leading to differences in metabolism and food preferences
.
In essence, adult obesity is a manifestation of multiple combined effects established in the early stages of development
The author said that the expression of these genes outside the hypothalamus is higher than that in the hypothalamus.
In the next step, researchers will continue to study the role of IRX3 and IRX5 in the brain
Obesity is one of the top ten chronic diseases identified by the World Health Organization.
Nearly 40% of people in the world are overweight and 13% are obese
.
Obese people are more likely to suffer from diabetes, cardiovascular disease and chronic kidney disease
.
In China, there are over 300 million people who are overweight and obese
.
FTO gene, obesity gene, means that the protein encoded by the gene is a component of a pathway that regulates appetite and energy balance, and the imbalance of this pathway directly or indirectly leads to the accumulation of body fat and weight gain
.
The strongest genetic association with obesity is a set of genetic variants in a gene called FTO
.
More than 40% of people have one copy of these variants, and 16% have two copies, which directly increases the risk of obesity by 70%
.
Despite their significant effects, the mechanisms by which these common variants lead to obesity remain unclear
.
On June 4, 2021, researchers from the University of Chicago published a research paper entitled "Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5" in the top international journal Science, which describes a set of genetic mutations.
Affect the expression of obesity-related genes in the brain and adipose tissue
.
Studies have found that changing the expression of obesity-related genes can produce behavioral changes
.
Mice lacking one of the genes reduced their interest in sweets
.
Changes in the expression of obesity-related genes are associated with changes in metabolism and behavior, indicating that the combined effects of these variants increase the risk of obesity
.
The researchers hope that this result will help to better understand the mechanisms that make some people more susceptible to obesity
.
The researchers first discovered that the genetic variation in the FTO gene physically interacted with the other two genes IRX3 and IRX5, indicating that these two genes may be related to obesity
.
Then, the researchers designed to knock out the IRX3 and IRX5 genes in mice and found that these mice were thinner, which proved that they are indeed related to obesity
.
Earlier, some scientists thought that FTO mutations may affect fat tissue or hypothalamus, so the research team wanted to know if it would be through the two genes IRX3 and IRX5
.
The researchers used a mouse model that lacked obesity-related regions in the FTO gene to observe the expression of IRX3 and IRX5 genes in different tissues of mice
.
The researchers found that the expression of IRX3 and IRX5 in adipose tissue and hypothalamus were reduced
.
Interestingly, this change in expression level only occurs during embryonic development, but not in adult tissues
.
Similar results have been seen in experiments with cultured human hypothalamic neurons
.
This suggests that obesity may be "natural"
.
To understand the role of these genes in the hypothalamus, the researchers used IRX3 knockout mice and investigated whether these mice had different eating behaviors
.
The researchers were surprised to find that mice lacking LRX3 had less interest in sweets
.
So, is this gene the same in humans? Researchers used data from the genetic testing service "23 and Me" and found that obesity-related FTO variants are also a powerful predictor of human sweet food preferences
.
This indicates that in addition to controlling metabolism, this gene also affects behavioral functions
.
The researchers showed that the FTO genome region actually contains multiple independent variants, which are all inherited together, and they each affect the expression of IRX3 and IRX5 in adipose tissue and hypothalamus, leading to differences in metabolism and food preferences
.
In essence, adult obesity is a manifestation of multiple combined effects established in the early stages of development
.
The author said that the expression of these genes outside the hypothalamus is higher than that in the hypothalamus.
In the next step, researchers will continue to study the role of IRX3 and IRX5 in the brain
.
( Yinuowei WeChat public account )
