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


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.”

Yoga and Meditation May Lead to an Inflated Ego

If you’ve been exasperated for years by that one self-righteous, yoga-obsessed friend, take note: Regular yoga practitioners experience inflated egos after a session of yoga or meditation, according to a forthcoming study in the journal Psychological Science.

Researchers found that yoga and meditation both increase "self-enhancement," or the tendency for people to attach importance to their own actions. In the first phase of the two-part study, researchers in Germany and England measured self-enhancement by recruiting 93 yoga students and having them respond to questionnaires over the course of 15 weeks, Quartz reports. Each assessment was designed to measure three outcomes: superiority, communal narcissism, and self-esteem. In the second phase, the researchers asked 162 meditation students to answer the same questionnaires over four weeks.

Participants showed significantly higher self-enhancement in the hour just after their practices. After yoga or meditation, participants were more likely to say that statements like "I am the most helpful person I know" and "I have a very positive influence on others" describe them.

At its Hindu and Buddhist roots, yoga is focused on quieting the ego and conquering the self. The findings seem to support what some critics of Western-style yoga suspect—that the practice is no longer true to its South Asian heritage.

It might not be all bad, though. Self-enhancement tends to correlate with higher levels of subjective well-being, at least in the short term. People prone to self-enhancement report feeling happier than the average person. However, they’re also more likely to exhibit social behaviors (like bragging or condescending) that are detrimental in the long term.

So if you think your yoga-loving friends are a little holier than thou, you may be right. But it might be because their yoga class isn’t deflating their egos like yogis say it should.

[h/t Quartz]

Doc_Brown, Flickr // CC BY-NC-ND 2.0. Cropped.
This Just In
The Honey Smacks In Your Pantry May Be Contaminated With Salmonella
Doc_Brown, Flickr // CC BY-NC-ND 2.0. Cropped.
Doc_Brown, Flickr // CC BY-NC-ND 2.0. Cropped.

Salmonella, a bacterial food-borne illness often associated with raw eggs and undercooked chicken, has been linked recently to a popular children's cereal. According to Snopes, the Centers for Disease Control and Prevention (CDC) is urging consumers to avoid Kellogg’s Honey Smacks, citing the brand as the likely cause of the Salmonella outbreak spreading across the U.S.

Since early March, 73 people in 31 states have contracted the virus. Salmonella clears up in most people on its own, but in some cases it can lead to hospitalization or even death. Twenty-four victims have been admitted to hospitals so far, with no reported deaths. Of the 39 patients who were questioned, 30 of them remembered eating cold cereal and 14 of them specifically cited Honey Smacks.

In response to the outbreak, the Kellogg Company has recalled its 15.3-ounce and 23-ounce boxes of Honey Smacks printed with any "best if used by" date between June 14, 2018 and June 14, 2019 (recalled boxes are labeled on the bottom with the UPC codes 3800039103 or 3800014810). The CDC recommends that you take even greater precautions by throwing out or returning any Honey Smacks you have at home, regardless of package size, "best by" date, or whether your family has eaten from the box previously without getting sick.

Symptoms of Salmonella include diarrhea, fever, headache, and abdominal pain, and usually appear 12 hours to three days after the contaminated food is ingested. If you or someone in your household is showing signs of the infection, ask a doctor about how to best treat it.

[h/t Snopes]


More from mental floss studios