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In recent years, Akkermansia muciniphila, the star of gut microbes, has been hot, and it has good improvement effects in host metabolism, immunity and intestinal barrier, cancer and neurological diseases [1-3] .
There have been many research results showing that Akk bacteria play an important role in the energy absorption, consumption and fat browning process in the host’s intestines.
However, how exactly Akk bacteria play a role has always puzzled researchers [4, 5] .
Recently, the team of Professor GwangPyo Ko of Seoul National University in South Korea published important research results on the mechanism of Akk bacteria improving host obesity and glucose homeostasis in the journal Nature.
They found the key to the many benefits of Akk bacteria, a protein, P9 [6].
This is the first time scientists have discovered the mechanism of Akk bacteria improving obesity.
The research team started this time with brown adipose tissue (BAT), the "electric blanket" of high-fat diet mice (HFD mice).
They found that administering Akk bacteria to HFD mice can increase the heat production of BAT (iBAT) between the scapula of the mice, which causes the skin temperature and rectal temperature of the mice to rise, which "burns" the calories of the mice and reduces the weight of the mice ! The researchers also tested the effect of Akk bacteria on white adipose tissue (WAT) and found that the Akk bacteria did not change the diameter and quality of the mouse WAT after administration of Akk bacteria to HFD mice, indicating that Akk bacteria only specifically affected HFD mice.
The thermogenic activity of mouse BAT thus suppresses obesity.
In addition, Akk bacteria also activates the secretion of the gastrointestinal hormone glucagon-like peptide 1 (GLP-1) in the intestine, regulates the energy balance of the host, and improves glucose homeostasis in mice.
After administration of Akk bacteria, the size and weight of iBAT decreased, and the number increased.
The expression of uncoupling protein 1 (Ucp1), which is responsible for regulating thermogenesis, increased.
Skin temperature and rectal temperature on iBAT increased.
In order to further clarify that Akk bacteria promote GLP What is the secreted active substance of -1? Researchers treated the cell-free supernatant and bacteria of cultured Akk bacteria separately to human intestinal secretory L cells (NCI-H716), and found that only the cell supernatant can promote the secretion of GLP-1.
At the same time, other 47 kinds of probiotics (lactic acid bacteria or bifidobacteria) were also used for testing, and no bacteria were found to have similar effects, indicating that this effect is unique to Akk bacteria.
Subsequently, the researchers conducted a series of separations of the substances secreted by Akk bacteria and applied these separated substances to NCI-H716 cells and found that a series of 100-300 kDa proteins can promote the secretion of GLP-1, among which the molecular weight The 84 kDa P9 protein has the strongest effect.
The previously reported results show that the outer membrane "star" protein of Akk bacteria, Amuc_1100, plays an important role in the process of Akk's beneficial effects on the host.
In order to verify whether Amuc_1100 can promote the secretion of GLP-1 like Akk, the researchers tested the expression of GLP-1 after treating NCI-H716 cells with Amuc_1100 and found that Amuc_1100 can also promote the secretion of GLP-1, but it is interesting that Amuc_1100 is The role of GLP-1 is almost "not worth mentioning" in front of the P9 protein! Among the isolated 100-300 kDa proteins, P1, P5 and P9 proteins can promote the secretion of GLP-1.
Among them, P9 shows a strong advantage.
Amuc_1100 was the first to find that its function in host metabolism is to inhibit obesity in mice.
Since P9 promotes GLP- The secretion of 1 is a thousand times stronger than Amuc_1100, so can P9 improve host obesity? What is the effect compared to Amuc_1100? With these problems in mind, the researchers administered the same doses of P1, P5, and P9 proteins to HFD mice and found that these proteins, like Amuc_1100, can improve mouse obesity and glucose homeostasis.Comparing the effect of these proteins with the effect of Amuc_1100 protein, it is found that P9 shows a stronger effect at the same dose! This discovery may shake the role of Amuc_1100 in improving host metabolic diseases.
The P9 protein secreted by Akk bacteria has a stronger effect on improving obesity and glucose homeostasis than Amuc_1100.
Further analysis revealed that the mechanism of P9-induced GLP-1 secretion is related to calcium ion signaling protein and intercellular adhesion molecule 2 (ICAM-2).
The cytokine interleukin 6 (IL-6) is usually related to the secretion of GLP-1.
The researchers found that P9 in IL-6 knockout mice could not promote the secretion of GLP-1, and it also eliminated the effect of P9 on improving glucose homeostasis.
effect.
In addition, after the GLP-1 receptor GLP-1R inhibitor EX9-39 and P9 protein were co-treated with HFD mice, it was found that the effect of P9 mice on improving mouse obesity and glucose homeostasis was eliminated.
These results clarify the mechanism by which the P9 protein improves host obesity and glucose homeostasis: After the P9 protein binds to its ligand ICAM-2, it activates the GLP-1R signaling pathway and IL-6 to promote thermogenesis and improve the obesity of HFD mice.
And glucose homeostasis.
In general, the research results explained for the first time the mechanism of Akk bacteria improving obesity from the perspective of brown adipose tissue, and discovered that a protein P9 secreted by Akk bacteria is the core of the role, which provides a new way for the development of therapeutic drugs for metabolic diseases.
Target.
However, although P9 has a positive effect on host metabolic diseases, if P9 is to play a role in HFD mice, it needs Akk bacteria to compete with other bacteria in HFD mice, and a larger number of Akk bacteria will secrete more.
There are many P9 proteins, which is undoubtedly challenging; if the P9 protein expressed in vitro is used as a drug, breakthroughs in the structure of the P9 protein and the structure of the P9 and ICAM-2 complex will be designed for the design of more effective therapeutic targets for metabolic diseases The development of P9 protein provides stronger evidence; in addition, if P9 protein is to be used in clinical treatment, the safety of P9 protein in the human body is also an issue that needs to be discussed and resolved urgently. References: [1] Plovier H.
, Everard A.
, Druart C.
, et al.
A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice[J].
Nat Med, 2017, 23( 1): 107-113.
[2] Wang L.
, Tang L.
, Feng Y.
, et al.
A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8(+) T cells in mice[J].
Gut, 2020, 69(11): 1988-1997.
[3] Routy B.
, Le Chatelier E.
, Derosa L.
, et al.
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J].
Science, 2018, 359(6371): 91-97.
[4] Gao X.
, Xie Q.
, Kong P.
, et al.
Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet- Induced Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice[J].
Infect Immun, 2018, 86(1).
[5] Depommier C.
,Van Hul M.
, Everard A.
, et al.
Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice[J].
Gut Microbes, 2020, 11(5): 1231-1245.
[ 6] Yoon HS, Cho CH, Yun MS, et al.
Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J].
Nat Microbiol, 2021, 6(5) : 563-573.
The author of this article | Wang Junchao, editor in charge | Dai SiyuAkkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J].
Nat Microbiol, 2021, 6(5): 563-573.
The author of this article | Wang Junchao, responsible editor | Daisi rainAkkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J].
Nat Microbiol, 2021, 6(5): 563-573.
The author of this article | Wang Junchao, responsible editor | Daisi rain
There have been many research results showing that Akk bacteria play an important role in the energy absorption, consumption and fat browning process in the host’s intestines.
However, how exactly Akk bacteria play a role has always puzzled researchers [4, 5] .
Recently, the team of Professor GwangPyo Ko of Seoul National University in South Korea published important research results on the mechanism of Akk bacteria improving host obesity and glucose homeostasis in the journal Nature.
They found the key to the many benefits of Akk bacteria, a protein, P9 [6].
This is the first time scientists have discovered the mechanism of Akk bacteria improving obesity.
The research team started this time with brown adipose tissue (BAT), the "electric blanket" of high-fat diet mice (HFD mice).
They found that administering Akk bacteria to HFD mice can increase the heat production of BAT (iBAT) between the scapula of the mice, which causes the skin temperature and rectal temperature of the mice to rise, which "burns" the calories of the mice and reduces the weight of the mice ! The researchers also tested the effect of Akk bacteria on white adipose tissue (WAT) and found that the Akk bacteria did not change the diameter and quality of the mouse WAT after administration of Akk bacteria to HFD mice, indicating that Akk bacteria only specifically affected HFD mice.
The thermogenic activity of mouse BAT thus suppresses obesity.
In addition, Akk bacteria also activates the secretion of the gastrointestinal hormone glucagon-like peptide 1 (GLP-1) in the intestine, regulates the energy balance of the host, and improves glucose homeostasis in mice.
After administration of Akk bacteria, the size and weight of iBAT decreased, and the number increased.
The expression of uncoupling protein 1 (Ucp1), which is responsible for regulating thermogenesis, increased.
Skin temperature and rectal temperature on iBAT increased.
In order to further clarify that Akk bacteria promote GLP What is the secreted active substance of -1? Researchers treated the cell-free supernatant and bacteria of cultured Akk bacteria separately to human intestinal secretory L cells (NCI-H716), and found that only the cell supernatant can promote the secretion of GLP-1.
At the same time, other 47 kinds of probiotics (lactic acid bacteria or bifidobacteria) were also used for testing, and no bacteria were found to have similar effects, indicating that this effect is unique to Akk bacteria.
Subsequently, the researchers conducted a series of separations of the substances secreted by Akk bacteria and applied these separated substances to NCI-H716 cells and found that a series of 100-300 kDa proteins can promote the secretion of GLP-1, among which the molecular weight The 84 kDa P9 protein has the strongest effect.
The previously reported results show that the outer membrane "star" protein of Akk bacteria, Amuc_1100, plays an important role in the process of Akk's beneficial effects on the host.
In order to verify whether Amuc_1100 can promote the secretion of GLP-1 like Akk, the researchers tested the expression of GLP-1 after treating NCI-H716 cells with Amuc_1100 and found that Amuc_1100 can also promote the secretion of GLP-1, but it is interesting that Amuc_1100 is The role of GLP-1 is almost "not worth mentioning" in front of the P9 protein! Among the isolated 100-300 kDa proteins, P1, P5 and P9 proteins can promote the secretion of GLP-1.
Among them, P9 shows a strong advantage.
Amuc_1100 was the first to find that its function in host metabolism is to inhibit obesity in mice.
Since P9 promotes GLP- The secretion of 1 is a thousand times stronger than Amuc_1100, so can P9 improve host obesity? What is the effect compared to Amuc_1100? With these problems in mind, the researchers administered the same doses of P1, P5, and P9 proteins to HFD mice and found that these proteins, like Amuc_1100, can improve mouse obesity and glucose homeostasis.Comparing the effect of these proteins with the effect of Amuc_1100 protein, it is found that P9 shows a stronger effect at the same dose! This discovery may shake the role of Amuc_1100 in improving host metabolic diseases.
The P9 protein secreted by Akk bacteria has a stronger effect on improving obesity and glucose homeostasis than Amuc_1100.
Further analysis revealed that the mechanism of P9-induced GLP-1 secretion is related to calcium ion signaling protein and intercellular adhesion molecule 2 (ICAM-2).
The cytokine interleukin 6 (IL-6) is usually related to the secretion of GLP-1.
The researchers found that P9 in IL-6 knockout mice could not promote the secretion of GLP-1, and it also eliminated the effect of P9 on improving glucose homeostasis.
effect.
In addition, after the GLP-1 receptor GLP-1R inhibitor EX9-39 and P9 protein were co-treated with HFD mice, it was found that the effect of P9 mice on improving mouse obesity and glucose homeostasis was eliminated.
These results clarify the mechanism by which the P9 protein improves host obesity and glucose homeostasis: After the P9 protein binds to its ligand ICAM-2, it activates the GLP-1R signaling pathway and IL-6 to promote thermogenesis and improve the obesity of HFD mice.
And glucose homeostasis.
In general, the research results explained for the first time the mechanism of Akk bacteria improving obesity from the perspective of brown adipose tissue, and discovered that a protein P9 secreted by Akk bacteria is the core of the role, which provides a new way for the development of therapeutic drugs for metabolic diseases.
Target.
However, although P9 has a positive effect on host metabolic diseases, if P9 is to play a role in HFD mice, it needs Akk bacteria to compete with other bacteria in HFD mice, and a larger number of Akk bacteria will secrete more.
There are many P9 proteins, which is undoubtedly challenging; if the P9 protein expressed in vitro is used as a drug, breakthroughs in the structure of the P9 protein and the structure of the P9 and ICAM-2 complex will be designed for the design of more effective therapeutic targets for metabolic diseases The development of P9 protein provides stronger evidence; in addition, if P9 protein is to be used in clinical treatment, the safety of P9 protein in the human body is also an issue that needs to be discussed and resolved urgently. References: [1] Plovier H.
, Everard A.
, Druart C.
, et al.
A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice[J].
Nat Med, 2017, 23( 1): 107-113.
[2] Wang L.
, Tang L.
, Feng Y.
, et al.
A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8(+) T cells in mice[J].
Gut, 2020, 69(11): 1988-1997.
[3] Routy B.
, Le Chatelier E.
, Derosa L.
, et al.
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J].
Science, 2018, 359(6371): 91-97.
[4] Gao X.
, Xie Q.
, Kong P.
, et al.
Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet- Induced Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice[J].
Infect Immun, 2018, 86(1).
[5] Depommier C.
,Van Hul M.
, Everard A.
, et al.
Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice[J].
Gut Microbes, 2020, 11(5): 1231-1245.
[ 6] Yoon HS, Cho CH, Yun MS, et al.
Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J].
Nat Microbiol, 2021, 6(5) : 563-573.
The author of this article | Wang Junchao, editor in charge | Dai SiyuAkkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J].
Nat Microbiol, 2021, 6(5): 563-573.
The author of this article | Wang Junchao, responsible editor | Daisi rainAkkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J].
Nat Microbiol, 2021, 6(5): 563-573.
The author of this article | Wang Junchao, responsible editor | Daisi rain
