-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Click on the blue word to follow us.
Genome-wide shows that increased alcohol consumption is associated with increased expression of FGF21 and KLB genes.
Animal experiments have shown that alcohol use can increase the expression level of FGF21 in the peripheral system, while exogenous increase of FGF21 can reduce alcohol consumption
.
The KLB gene encodes the protein β-klotho, which is the main part of the endocrine fibroblast growth factor 21 (FGF21) receptor complex.
The combination of the two stimulates insulin sensitivity and causes weight loss
.
FGF21 is produced by the liver, acts on adipose and pancreatic tissue, can pass through the blood-brain barrier, and plays a key role in regulating energy metabolism
.
On February 1, 2022, the research team of Matthew J.
Potthoff of the University of Iowa revealed that the increase of FGF21 caused by alcohol use is mainly produced by the liver, and FGF21 can specifically act on the projection of KLB-positive neurons in the BLA brain region to the nucleus accumbens.
neural circuits
.
Figure 1: FGF21 Recombinant Protein Reduces Alcohol Intraperitoneal injection of human-derived FGF21 recombinant protein or a small molecule analog of FGF21, PF-05231023, significantly reduces alcohol use in mice, and vervet monkeys can also suppress alcohol use after receiving PF-05231023 injection Alcohol intake (Figure 1)
.
The researchers were able to promote alcohol use by virus-specifically knocking out FGF21 in the liver of mice
.
Furthermore, alcohol consumption did not increase peripheral blood FGF21 levels after knockout of hepatic FGF21, these results suggest that the elevation of FGF21 induced by alcohol consumption is mainly produced by the liver
.
In order to further search for the target of FGF21 in the peripheral system in the brain, they found that the basolateral amygdala (BLA) region highly expressed KLB through the KLB-cre tool mouse
.
Injection of FGF21 recombinant protein or PF-05231023 into the BLA brain region significantly reduced alcohol consumption, and knockout of KLB blocked this effect of reducing alcohol use
.
Electrophysiological experiments found that incubation with FGF21 could depolarize the resting membrane potential and increase the membrane resistance of KLB-positive neurons in the BLA brain region, showing increased excitability
.
Figure 2: Anterograde and retrograde tracer viruses reveal the KLB BLA→NAc circuit Anterograde virus tracer experiments found that KLB-positive neurons in the BLA brain region project to the nucleus accumbens (NAc, hereinafter referred to as the KLB BLA→NAc circuit), Retrograde tracer virus also confirmed the existence of projective connections between these two brain regions
.
In vitro brain slice experiments showed that incubation of FGF21 can specifically excite this neural circuit
.
The NAc brain area mainly includes dopamine type 1 and 2 receptors in the middle spine neurons, and the projection of the BLA brain area to the NAc regulates reward behavior and goal motivation behavior through the excitation of the middle spine neurons
.
FGF21 enhances spontaneous excitatory postsynaptic currents at dopamine type 2 receptors (but not type 1 receptors) in the NAc brain region
.
After the researchers specifically knocked out KLB expression on the BLA→NAc loop through a two-virus strategy, the reduction of alcohol consumption caused by injection of FGF21 recombinant protein or PF-05231023 could be significantly blocked; after restoring KLB expression by virus, FGF21 could play a role in reducing alcohol consumption.
Effects of alcohol use
.
This suggests that the expression of KLB in the BLA region is necessary for FGF21 to exert its inhibition on alcohol consumption
.
Collectively, this paper reveals that liver-derived FGF21 limits alcohol use through the brain BLA→NAc loop
.
This is dependent on β-klotho protein
.
[References] 1.
https://doi.
org/10.
1016/j.
cmet.
2021.
12.
024 The pictures in the text are from references
Genome-wide shows that increased alcohol consumption is associated with increased expression of FGF21 and KLB genes.
Animal experiments have shown that alcohol use can increase the expression level of FGF21 in the peripheral system, while exogenous increase of FGF21 can reduce alcohol consumption
.
The KLB gene encodes the protein β-klotho, which is the main part of the endocrine fibroblast growth factor 21 (FGF21) receptor complex.
The combination of the two stimulates insulin sensitivity and causes weight loss
.
FGF21 is produced by the liver, acts on adipose and pancreatic tissue, can pass through the blood-brain barrier, and plays a key role in regulating energy metabolism
.
On February 1, 2022, the research team of Matthew J.
Potthoff of the University of Iowa revealed that the increase of FGF21 caused by alcohol use is mainly produced by the liver, and FGF21 can specifically act on the projection of KLB-positive neurons in the BLA brain region to the nucleus accumbens.
neural circuits
.
Figure 1: FGF21 Recombinant Protein Reduces Alcohol Intraperitoneal injection of human-derived FGF21 recombinant protein or a small molecule analog of FGF21, PF-05231023, significantly reduces alcohol use in mice, and vervet monkeys can also suppress alcohol use after receiving PF-05231023 injection Alcohol intake (Figure 1)
.
The researchers were able to promote alcohol use by virus-specifically knocking out FGF21 in the liver of mice
.
Furthermore, alcohol consumption did not increase peripheral blood FGF21 levels after knockout of hepatic FGF21, these results suggest that the elevation of FGF21 induced by alcohol consumption is mainly produced by the liver
.
In order to further search for the target of FGF21 in the peripheral system in the brain, they found that the basolateral amygdala (BLA) region highly expressed KLB through the KLB-cre tool mouse
.
Injection of FGF21 recombinant protein or PF-05231023 into the BLA brain region significantly reduced alcohol consumption, and knockout of KLB blocked this effect of reducing alcohol use
.
Electrophysiological experiments found that incubation with FGF21 could depolarize the resting membrane potential and increase the membrane resistance of KLB-positive neurons in the BLA brain region, showing increased excitability
.
Figure 2: Anterograde and retrograde tracer viruses reveal the KLB BLA→NAc circuit Anterograde virus tracer experiments found that KLB-positive neurons in the BLA brain region project to the nucleus accumbens (NAc, hereinafter referred to as the KLB BLA→NAc circuit), Retrograde tracer virus also confirmed the existence of projective connections between these two brain regions
.
In vitro brain slice experiments showed that incubation of FGF21 can specifically excite this neural circuit
.
The NAc brain area mainly includes dopamine type 1 and 2 receptors in the middle spine neurons, and the projection of the BLA brain area to the NAc regulates reward behavior and goal motivation behavior through the excitation of the middle spine neurons
.
FGF21 enhances spontaneous excitatory postsynaptic currents at dopamine type 2 receptors (but not type 1 receptors) in the NAc brain region
.
After the researchers specifically knocked out KLB expression on the BLA→NAc loop through a two-virus strategy, the reduction of alcohol consumption caused by injection of FGF21 recombinant protein or PF-05231023 could be significantly blocked; after restoring KLB expression by virus, FGF21 could play a role in reducing alcohol consumption.
Effects of alcohol use
.
This suggests that the expression of KLB in the BLA region is necessary for FGF21 to exert its inhibition on alcohol consumption
.
Collectively, this paper reveals that liver-derived FGF21 limits alcohol use through the brain BLA→NAc loop
.
This is dependent on β-klotho protein
.
[References] 1.
https://doi.
org/10.
1016/j.
cmet.
2021.
12.
024 The pictures in the text are from references
