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Therapeutic Pathway to Treat Alcoholism

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Therapeutic Pathway to Treat Alcoholism

A liver hormone called FGF21 may regulate alcohol drinking by acting directly on a receptor in the brain, according to a new study.  This raises the possibility of a new therapeutic pathway that could one day be targeted to reduce the desire for alcohol in problem drinkers. The new study, by researchers from Imperial College London, King’s College London, and UT Southwestern Medical Center, for the first time highlights a liver-brain axis which plays an important role in regulating the consumption of alcohol. Alcohol drinking is a complex trait that is known to be partly inherited, yet so far there have been few genes associated with it.

 

Genetic influences on brain functions that affect drinking behaviour have been difficult to detect because the effect of individual genes is so small, so large studies are required to detect the genetic signal. In this new study, published today in Proceedings of National Academy of Sciences (PNAS), researchers carried out the largest-ever genetic analysis of usual (i.e. non-addictive) alcohol consumption in more than 105,000 individuals of European descent. In addition to providing samples for genetic analysis, the participants answered questionnaires on their weekly drinking habits.

They found variations of a gene called β-Klotho that were related to the amount of alcohol people were consuming, indicating that this gene may regulate drinking behaviour. The less frequent variant – seen in approximately 40 percent of people in the study – was associated with a decreased desire to drink alcohol.

To examine whether β-Klotho affects alcohol drinking in mice, and whether it does so through actions in the brain, they also measured alcohol intake and alcohol preference of mice in which β-Klotho had been removed. They found that mice lacking β-Klotho in the brain showed significantly increased alcohol preference and consumption compared to mice with β-Klotho, indicating that intact β-Klotho might help to control alcohol intake.

Under normal conditions FGF21 inhibits alcohol preference in mice. However, when these mice were lacking β-Klotho, FGF21 had no effect on drinking behaviour, suggesting that FGF21’s effects on alcohol consumption depend on β-Klotho expression in the brain. The researchers also found that mice lacking β-Klotho did not show any difference in measures of anxiety, which might influence drinking behaviour, compared to mice with β-Klotho.

Professor Gunter Schumann from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, said: ‘Our study reveals a previously unrecognised liver-brain pathway which regulates alcohol consumption in humans, and which could one day be targeted therapeutically to suppress consumption in problem drinkers.

‘The results point towards an intriguing feedback loop, where FGF21 is produced in the liver in response to sugar and alcohol intake, which then acts directly on the brain to limit consumption.’

Professor Schumann added: ‘We cannot rule out the possibility that β-Klotho acts by affecting neighbouring genes, so further genetic studies are warranted. It will also be important to explore these findings in more severe forms of alcohol drinking, as we only examined non-addictive consumption.’

Professor Paul Elliott from the School of Public Health at Imperial said: "Alcohol drinking in excess is a major public health problem worldwide and we need to find new ways of reducing the harmful effects of alcohol in the population. Even small shifts downward in the average amount of alcohol people drink may have major health benefits."

He added: "The results of our study point to a previously unrecognised genetic determinant of alcohol drinking among the general population. Our findings may eventually lead to new treatments for people whose health is being harmed by drinking."


This study was funded by the Medical Research Council, the European Commission and the Howard Hughes Medical Institute.

"KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference" is published in PNAS

Adapted from a press release by King's College London
Kate Wighton
Communications and Public Affairs

See the press release of this article

Article text (excluding photos or graphics) available under an Attribution-NonCommercial-ShareAlike Creative Commons license.

Read 385 times Last modified on Saturday, 24 December 2016 13:07
Rich Wermske

My pedigree and bona fides are published elsewhere. That said, I respect that a few may wish to learn more about the private person behind the writing.  While I accept I am exceptionally introverted (tending toward the misanthropic), I do enjoy socializing and sharing time with like-minded individuals. I have a zeal for integrity, ethics, and the economics of both interpersonal and organizational behavior.

The product of multi-generational paternal dysfunction, I practice healthy recovery (sobriety date December 11, 2001).  I am endogamous in my close personal relationships and belong to a variety of tribes that shape my worldview (in no particular order):

☯ I participate in and enjoy most geek culture. ☯ I am a practicing Buddhist and a legally ordained minister. I like to believe that people of other spiritual/faith systems find me approachable.  I am a member of the GLBTQA community -- I married my long-time partner in a ceremony officiated by Jeralita "Jeri" Costa of Joyful Joinings on November 18, 2013, certificated in King County, Seattle WA. We celebrate an anniversary date of February 2, 2002.  I am a service-connected, disabled, American veteran (USAF).  I am a University of Houston alumnus (BBA/MIS) and currently studying as a post baccalaureate for an additional degree in Philosophy and Law, Values, & Policy.  I am a retired Bishop in the Church of Commerce and Capitalism; the story arch of my prosecuting and proselytizing the technological proletariat is now behind me.  I am a native Houstonian (and obviously Texan).  At 50 years old, I am a "child of the sixties" and consider the 80's to be my formative years.

As I still struggle with humility, I strive to make willingness, honesty, and open mindedness cornerstones in all my affairs. Fourteen years of sobriety has taught me that none of "this" means a thing if I'm unwilling, dishonest, or close minded.  Therefore I work hard on the things I believe in --

  • I believe we can always achieve more if we collaborate and compromise.
  • I believe that liberal(ism) is a good word/concept and something to be proud to support.  The modern, systematic corruption of liberal ideas is a living human tragedy.
  • I believe in a worldview founded on ideas of liberty and equality. The pragmatism of this site and my journey is rooted in both classical and social liberalism.
  • I believe in democratic elections and institutions including a media free of commercial and governmental bias.  Liberty and equality perish when a society becomes uneducated and/or ill-informed.
  • I believe in diversity of life and ideas.  Life and ideas can only flourish when the gene pool is vast and abundantly differentiated.
  • I believe in advancing balance in civil, social, and privacy rights such that all of humanity is continuously uplifted.
  • I believe in separation of church (spirituality) and state (governance) -- with neither in supremacy nor subjugation.
  • I believe in private (real or tangible) property explicitly excluding ideas, knowledge, and methods; such non-tangibles, by natural law, being free for all humanity and emancipated at conception.

While change and the uncertainty of the future may be uncomfortable, I do not fear the unknown; therefore:

    • I believe I must be willing to make difficult choices, that those choices may not be all that I desire, and that such may result in undesirable (or unintended) consequences;
    • I believe we must be willing to make mistakes or be wrong; and I am willing to change my mind if necessary.
I undertake to abide the five precepts of Buddhism; therefore:
  1. I believe it is wrong to kill or to knowingly allow others to kill.
  2. I believe it is wrong to steal or to knowingly allow others to steal.
  3. I believe in abstention from sexual misconduct.
  4. I believe it is wrong to lie or to knowingly allow others to lie.
  5. I believe in abstention from non-medicinal intoxicants as such clouds the mind.

Suicide, major depression, borderline personality, and alcoholism are feral monsters ever howling at my doorstep. However, despite my turbulent and tragic past, rare is the day where I have to rationalize, defend, or justify the actions of that person I see looking back at me in the mirror...

Website: www.wermske.com
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