CLOSE
iStock
iStock

Liver Stress Hormone Talks to the Brain to Reduce Alcohol and Sugar Preference

iStock
iStock

Endocrinology researchers already knew that a stress hormone secreted in the liver—fibroblast growth factor 21, or FGF21—helps regulate metabolism in humans and mice. Now, a new study published by researchers at UT Southwestern Medical Center in Cell Metabolism is the first to discover that FGF21 communicates directly with the brain via the brain’s reward pathway to control preferences for, and amounts of, sugar and alcohol consumption in mice—and potentially humans. This could lead to new drugs to treat diabetes, alcoholism, and other forms of addiction. 

Though the new study was conducted on mice, co-senior author Steven Kliewer, a professor of molecular biology and pharmacology at UT Southwestern, tells mental_floss: “Our springboard for this study was human studies. One of the nice things about this is that we already have evidence of human relevance, not just a rodent phenomenon.” 

Kliewer runs a joint laboratory with David Mangelsdorf, with whom he has done four total studies on FGF21. Two studies published in Nature Medicine in 2013 showed FGF21’s ability to regulate metabolism, circadian behavior, and female reproduction. In 2014, their study published in Cell Metabolism showed that FGF21 can cause weight loss. 

Kliewer and Mangelsdorf knew the liver releases FGF21 in response to a variety of stresses, such as marked changes in metabolic and environmental stresses that accompany starvation or exposure to extreme cold, but, Kliewer says, “We hadn’t anticipated that there would be this endocrine loop where the liver communicates with the brain to regulate nutrient preference.”

FGF21 sends the message “too much” to the brain when it is consuming sugar or alcohol, “but obviously it’s not enough to stop overconsumption in the long run,” Kliewer says. At least, not yet. He believes that the FGF21 pathway “could be very powerful to exploit in terms of developing drugs to treat addiction.”

The researchers demonstrated that mice with elevated levels of FGF21 showed a reduced preference for either sweetener- or ethanol-laced water. The mice were given “free access” to food and a choice between two water bottles in their cages. In the first experiment, one of the bottles contained only water and the other contained sweetened water. They repeated the experiment with two bottles of water and one with concentrations of ethanol. Then they measured how much the mice drank from each bottle.  

They were surprised to find that the FGF21 mice showed reduced interest in either the sweetened or the ethanol water, and preferred plain water. Furthermore, they showed that FGF21 was responsible for the decreased preference for sweet and alcohol in the brain, accompanied by a decrease in dopamine levels. “We found that FGF21 affects neurotransmitter dopamine levels, which is important for lots of reward behaviors, it’s a global reward regulator,” Kleiwer says. 

FGF21 requires a co-receptor, β-Klotho, to function. To confirm that FGF21 acts along the brain’s reward pathway, they increased its levels in mice that had been genetically modified to be unable to produce β-Klotho and found the taste preference effect disappeared. 

From here they hope to understand the molecular pathways of FGF21 better for its drug potential in the treatment of addiction, which will require more study due to its known side effects. “We already know that it causes some bone loss when it’s taken long term at high levels,” says Kliewer. “And any time you start messing around with reward behaviors, you have to worry about depression.” 

Kliewer says that the questions driving the next phase of research will include: “What is the reason the liver does this [secretes FGF21 along the brain’s reward pathway]? Under what conditions naturally? And can the levels of FGF21 be increased in humans?”

He cautions that it's a long process to bring research findings into clinical settings. “This is exciting biology and has promise, but … people have to take this [finding] with a grain of salt.”

nextArticle.image_alt|e
iStock
arrow
language
The Surprising Link Between Language and Depression
iStock
iStock

Skim through the poems of Sylvia Plath, the lyrics of Kurt Cobain, or posts on an internet forum dedicated to depression, and you'll probably start to see some commonalities. That's because there's a particular way that people with clinical depression communicate, whether they're speaking or writing, and psychologists believe they now understand the link between the two.

According to a recent study published in Clinical Psychological Science, there are certain "markers" in a person's parlance that may point to symptoms of clinical depression. Researchers used automated text analysis methods to comb through large quantities of posts in 63 internet forums with more than 6400 members, searching for certain words and phrases. They also noted average sentence length, grammatical patterns, and other factors.

What researchers found was that a person's use (or overuse) of first-person pronouns can provide some insight into the state of their mental health. People with clinical depression tend to use more first-person singular pronouns, such as "I" and "me," and fewer third-person pronouns, like "they," "he," or "she." As Mohammed Al-Mosaiwi, a Ph.D. candidate in psychology at the University of Reading and the head of the study, writes in a post for IFL Science:

"This pattern of pronoun use suggests people with depression are more focused on themselves, and less connected with others. Researchers have reported that pronouns are actually more reliable in identifying depression than negative emotion words."

What remains unclear, though, is whether people who are more focused on themselves tend to depression, or if depression turns a person's focus on themselves. Perhaps unsurprisingly, people with depression also use more negative descriptors, like "lonely" and "miserable."

But, Al-Mosaiwi notes, it's hardly the most important clue when using language to assess clinical depression. Far better indicators, he says, are the presence of "absolutist words" in a person's speech or writing, such as "always," "constantly," and "completely." When overused, they tend to indicate that someone has a "black-and-white view of the world," Al-Mosaiwi says. An analysis of posts on different internet forums found that absolutist words were 50 percent more prevalent on anxiety and depression forums, and 80 percent more prevalent on suicidal ideation forums.

Researchers hope these types of classifications, supported by computerized methods, will prove more and more beneficial in a clinical setting.

[h/t IFL Science]

nextArticle.image_alt|e
iStock
arrow
Health
Just 5 Alcoholic Drinks a Week Could Shorten Your Lifespan
iStock
iStock

Wine lovers were elated when a scientific study last year suggested that drinking a glass of wine a day could help them live longer. Now a new study, published in The Lancet, finds that having more than 100 grams of alcohol a week (the amount in about five glasses of wine or pints of beer) could be detrimental to your health.

Researchers from the University of Cambridge and the British Heart Foundation studied the health data of nearly 600,000 drinkers in 19 countries and found that five to 10 alcoholic drinks a week (yes, red wine included) could shave six months off the life of a 40-year-old.

The penalty is even more severe for those who have 10 to 15 drinks a week (shortening a person’s life by one to two years), and those who imbibe more than 18 drinks a week could lose four to five years of their lives. In other words, your lifespan could be shortened by half an hour for every drink over the daily recommended limit, according to The Guardian, making it just as risky as smoking.

"The paper estimates a 40-year-old drinking four units a day above the guidelines [the equivalent of drinking three glasses of wine in a night] has roughly two years' lower life expectancy, which is around a 20th of their remaining life," David Spiegelhalter, a statistician at the University of Cambridge who was not involved with the study, tells The Guardian. "This works out at about an hour per day. So it's as if each unit above guidelines is taking, on average, about 15 minutes of life, about the same as a cigarette."

[h/t The Guardian]

SECTIONS

arrow
LIVE SMARTER
More from mental floss studios