Treatment keeps alcoholic monkeys from drinking as much

Date:
February 1, 2022
Source:
Cell Press
Summary:
A hormone produced by the liver called fibroblast growth factor
21 (FGF21) suppresses alcohol consumption in primates, finds a
new study.

Vervet monkeys with a strong preference for ethanol that were given
an FGF21 analogue consumed 50% less alcohol. The study also studied
the brain circuits involved in mice and found that the protein,
known to also reduce sugar intake, acts on different circuits to
reduce alcohol and sugar consumption.



FULL STORY ==========================================================================
A hormone produced by the liver called fibroblast growth factor 21 (FGF21) suppresses alcohol consumption in primates, finds a study published
February 1 in the journal Cell Metabolism. Vervet monkeys with a strong preference for ethanol that were given an FGF21 analogue consumed 50%
less alcohol. The study also studied the brain circuits involved in
mice and found that the protein, known to also reduce sugar intake,
acts on different circuits to reduce alcohol and sugar consumption.


========================================================================== "When considering how and why these modality specific mechanisms
evolved, it is interesting to note that mammals were primarily exposed
to alcohol from fermenting fruits, which possess high levels of simple
sugars," says senior study author Matthew Potthoff (@potthofflab)
of the University of Iowa Carver College of Medicine. "Despite this,
neural circuits regulating FGF21-mediated suppression of sugar and
alcohol intake apparently developed independently and not in response
to a shared selective pressure." Excessive alcohol consumption is
a major health and social issue in our society. Given that excessive
alcohol consumption negatively impacts health and survival, it is not surprising that numerous physiological systems have evolved to sense
and regulate it in mammals. Unfortunately, efforts to therapeutically
target pathways that regulate alcohol consumption have been limited in
their ability to effectively treat alcohol use disorder.

Recently, genome-wide association studies have shown that FGF21
genetic variants are linked to increased alcohol consumption in
humans. In rodents, pharmacologic administration of this protein,
which is produced in the liver, reduces alcohol consumption through
actions in the brain. But until now, the neural circuits through which
FGF21 inhibits alcohol consumption were unknown, as were its effects on
alcohol consumption in higher organisms.

In the new study, Potthoff and co-first author Kyle Flippo of the
University of Iowa and international collaborators, including co-first
authors Drs. Matthew Gillum and Samuel Trammell of the University of Copenhagen, showed that administration of an FGF21 analogue reduces
alcohol intake by 50% in vervet monkeys with a strong innate preference
for ethanol. FGF21 and the FGF21 analogue decrease alcohol intake even
when administered after prolonged ethanol exposure in mice and primates.

FGF21 alters neural transmission in the nucleus accumbens, a brain
region that plays a complex role in reward and addiction, and suppresses alcohol consumption through a sub-population of neurons in the basolateral amygdala.

Specifically, FGF21 signaling in neurons that project from the
basolateral amygdala to the nucleus accumbens suppresses alcohol
consumption by changing the activity of a specific subpopulation of
these neurons. Previous studies have shown that this pathway is involved
in reward-seeking behavior. According to the authors, more research is
needed to investigate the specific effects of FGF21 on the activity of
these neurons during alcohol consumption in animal models.

"Our results provide a mechanism for a liver-to-brain endocrine
feedback loop that presumably functions to protect the liver from
damage," Flippo says. "The central molecular and cellular effects
of FGF21 represent an opportunity for future research, and the
present data indicates that FGF21 analogues may provide a potential
treatment option against alcohol-use disorder and related diagnosis."
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edited for style and length.


========================================================================== Journal Reference:
1. Kyle H. Flippo, Samuel A.J. Trammell, Matthew P. Gillum, Iltan
Aklan,
Misty B. Perez, Yavuz Yavuz, Nicholas K. Smith, Sharon
O. Jensen-Cody, Bolu Zhou, Kristin E. Claflin, Amy Beierschmitt,
Anders Fink-Jensen, Filip K. Knop, Roberta M. Palmour, Brad
A. Grueter, Deniz Atasoy, Matthew J. Potthoff. FGF21 suppresses
alcohol consumption through an amygdalo- striatal circuit. Cell
Metabolism, 2022; 34 (2): 317 DOI: 10.1016/ j.cmet.2021.12.024 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220201110624.htm

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