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

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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.”

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Animals
Owning a Dog May Add Years to Your Life, Study Shows
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We've said that having a furry friend can reduce depression, promote better sleep, and encourage more exercise. Now, research has indicated that caring for a canine might actually extend your lifespan.

Previous studies have shown that dog owners have an innate sense of comfort and increased well-being. A new paper published in Scientific Reports and conducted by Uppsala University in Sweden looked at the health records of 3.4 million of the country's residents. These records typically include personal data like marital status and whether the individual owns a pet. Researchers got additional insight from a national dog registry providing ownership information. According to the study, those with a dog for a housemate were less likely to die from cardiovascular disease or any other cause during the study's 12-year duration.

The study included adults 40 to 80 years old, with a mean age of 57. Researchers found that dogs were a positive predictor in health, particularly among singles. Those who had one were 33 percent less likely to die early than those who did not. Authors didn't conclude the exact reason behind the correlation: It could be active people are more likely to own dogs, that dogs promoted more activity, or that psychological factors like lowered incidences of depression might bolster overall well-being. Either way, having a pooch in your life could mean living a longer one.

[h/t Bloomberg]

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Live Smarter
Not Sure About Your Tap Water? Here's How to Test for Contaminants
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In the wake of Flint, Michigan's water crisis, you may have begun to wonder: Is my tap water safe? How would I know? To put your mind at ease—or just to satisfy your scientific curiosity—you can find out exactly what's in your municipal water pretty easily, as Popular Science reports. Depending on where you live, it might even be free.

A new water quality test called Tap Score, launched on Kickstarter in June 2017, helps you test for the most common household water contaminants for $120 per kit. You just need to take a few samples, mail them to the lab, and you'll get the results back in 10 days, telling you about lead levels, copper and cadmium content, arsenic, and other common hazardous materials that can make their way into water via pipes or wells. If you're mostly worried about lead, you can get a $40 test that only tells you about the lead and copper content of your water.

In New York State, a free lead-testing program will send you a test kit on request that allows you to send off samples of your water to a state-certified lab for processing, no purchase required. A few weeks later, you'll get a letter with the results, telling you what kind of lead levels were found in your water. This option is great if you live in New York, but if your state doesn't offer free testing (or only offers it to specific locations, like schools), there are other budget-friendly ways to test, too.

While mailing samples of your water off to a certified lab is the most accurate way to test your water, you can do it entirely at home with inexpensive strip tests that will only set you back $10 to $15. These tests aren't as sensitive as lab versions, and they don't test for as many contaminants, but they can tell you roughly whether you should be concerned about high levels of toxic metals like lead. The strip tests will only give you positive or negative readings, though, whereas the EPA and other official agencies test for the concentration of contaminants (the parts-per-billion) to determine the safety of a water source. If you're truly concerned with what's in your water, you should probably stick to sending your samples off to a professional, since you'll get a more detailed report of the results from a lab than from a colored strip.

In the future, there will likely be an even quicker way to test for lead and other metals—one that hooks up to your smartphone. Gitanjali Rao, an 11-year-old from Colorado, won the 2017 Young Scientist Challenge by inventing Tethys, a faster lead-testing device than what's currently on the market. With Tethys, instead of waiting for a lab, you can get results instantly. It's not commercially available yet, though, so for now, we'll have to stick with mail-away options.

[h/t Popular Science]

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