October 3, 2022

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Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%



 

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%

 

It is well known that drinking alcohol is harmful to health . Excessive drinking will have a negative impact on physical health and induce a series of chronic diseases , such as atherosclerosis, cardiovascular and cerebrovascular diseases, nervous system diseases, and even increase the risk of various cancers such as gastric cancer and liver cancer. .

 

Alcohol use disorder (AUD) , characterized by chronic relapse over time after abstinence from alcohol, has become one of the major public health problems worldwide.

The most important way to successfully treat alcohol use disorder is to prevent high alcohol cravings and relapses.

Unfortunately, there are currently no satisfactory medical interventions to prevent alcohol addiction relapse.

 

Interestingly, human and primate livers can produce a hormone called fibroblast growth factor 21 (FGF21) , which inhibits alcohol intake in primates. However, the neural circuits that signal FGF21 to inhibit alcohol intake remain unclear.

 

Recently, researchers from the University of Iowa Carver School of Medicine published in the Cell sub-journal Cell Metabolism : FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit research paper.

 

The study showed that injecting nonhuman primates with FGF21 and its analogs reduced alcohol intake by 50 percent .

In addition, the researchers found that FGF21 controls drinking through a subset of KLB-expressing neurons in the basolateral amygdala of the brain, thus demonstrating the potential of FGF21 to treat excessive drinking.

 

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%

 

 

 Interestingly, scientists have found that wine is not unique to humans. Mammals learned to consume alcohol from fermented fruits long before humans invented the winemaking process.

 

Considering the negative effects of excessive drinking on health and survival, it is not surprising that mammals have evolved corresponding physiological systems to sense and regulate alcohol intake.

In recent years, scientists have discovered through genome-wide association studies that multiple single-nucleotide polymorphisms (SNPs) in the FGF21 and KLB genes are associated with increased drinking in humans.

 

Professor Matthew Potthoff , from the University of Iowa’s Carver School of Medicine, said: “In considering how and why these specific mechanisms evolved, it is interesting that the neural circuits regulating FGF21-mediated inhibition of sugar and alcohol intake apparently arose independently. rather than responding to shared selection pressures.”

 

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%Schematic diagram of this study

 

 

FGF21 is produced by the liver in response to metabolic and nutritional challenges, it can be transmitted across the blood-brain barrier to the central nervous system, and has functions to regulate energy homeostasis and macronutrient balance.

In addition, several studies have found that delivering FGF21 directly to the central nervous system of mice can reduce their alcohol preference.

 

But unfortunately, while scientists have found that dopamine levels in the brain are affected by FGF21, it is unclear which neural circuit FGF21 uses to mediate the inhibition of alcohol consumption.

 

In this latest study, the research team found that the use of FGF21 and its analogs reduced the use of FGF21 and its analogs in the non-human primate with a strong innate preference for alcohol, the West African green monkey ( Chlorocebus sabaeus ) , by 50% alcohol intake.

 

Not only that, but injection of FGF21 and FGF21 analogs significantly reduced alcohol intake in experimental animals, even in mice and primates that had become alcohol-dependent due to chronic alcohol exposure.

 

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%FGF21 and its analogs inhibit alcohol intake in West African green monkeys

 

 

The research team further explored the neural mechanism by which FGF21 and FGF21 analogs produce the inhibitory effect of alcohol.

The researchers found that FGF21 alters glutamate transmission in the nucleus accumbens , a brain region with complex roles in reward and addiction, and is inhibited by a subset of KLB-expressing neurons in the basolateral amygdala Alcohol intake.

 

FGF21 alters glutamate transmission in the nucleus accumbens

 

 

Briefly, FGF21 signaling in neurons projecting from the basolateral amygdala to the nucleus accumbens inhibits alcohol intake by altering the activity of specific subsets of these neurons.

The authors say more research is needed to reveal the specific effects of FGF21 on the activity of these neurons in experimental animals with alcohol preference.

 

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%
FGF21 signals KLB-expressing neurons in the basolateral amygdala to inhibit alcohol intake

 

 

Dr. Kyle Flippo , one of the corresponding authors of the study , said: “The findings provide a mechanism for a liver-to-brain endocrine feedback loop that presumably functions to protect the liver from damage .

The central molecular and cellular effects of FGF21 are Future research presents an opportunity, and current data suggest that FGF21 analogs may offer a potential therapeutic option for alcohol use disorder and related diagnoses. “

 

 

 

 

 

 

Reference :
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00690-2

Cell Metabolism: This hormone produced in the liver reduces alcohol intake by 50%

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