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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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Big Questions
What Is the Difference Between Generic and Name Brand Ibuprofen?
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What is the difference between generic ibuprofen vs. name brands?

Yali Friedman:

I just published a paper that answers this question: Are Generic Drugs Less Safe than their Branded Equivalents?

Here’s the tl;dr version:

Generic drugs are versions of drugs made by companies other than the company which originally developed the drug.

To gain FDA approval, a generic drug must:

  • Contain the same active ingredients as the innovator drug (inactive ingredients may vary)
  • Be identical in strength, dosage form, and route of administration
  • Have the same use indications
  • Be bioequivalent
  • Meet the same batch requirements for identity, strength, purity, and quality
  • Be manufactured under the same strict standards of FDA's good manufacturing practice regulations required for innovator products

I hope you found this answer useful. Feel free to reach out at www.thinkbiotech.com. For more on generic drugs, you can see our resources and whitepapers at Pharmaceutical strategic guidance and whitepapers

This post originally appeared on Quora. Click here to view.

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Health
8 Potential Signs of a Panic Attack
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It's not just fear or worry. In fact, many panic attacks don’t look like panic at all. Panic attacks come on rapidly, and often at times that don't seem to make sense. The symptoms of panic disorder vary from person to person and even from attack to attack for the same person. The problems listed below are not unique to panic attacks, but if you're experiencing more than one, it's a good idea to talk to your doctor either way.

1. YOU'RE DIZZY.

Doctors sometimes call the autonomic nervous system (ANS) the "automatic nervous system" because it regulates many vital bodily functions like pumping blood all on its own, without our having to think about it. Panic attacks often manifest through the ANS, leading to increased heart rate or decreased blood pressure, which can in turn lead to feeling lightheaded or faint.

2. YOU'RE LOSING YOURSELF.

Feeling detached from yourself is called depersonalization. Feeling detached from the world, or like it's fake or somehow unreal, is called derealization. Both forms of dissociation are unsettling but common signs that a panic attack has begun.

3. YOU'RE QUEASY.

Our digestive system is often the first body part to realize that something is wrong. Panic sends stress hormones and tension to the gut and disrupts digestion, causing nausea, upset stomach, or heartburn.

4. YOU FEEL NUMB OR TINGLY.

Panic attacks can manifest in truly surprising ways, including pins and needles or numbness in a person's hands or face.

5. YOU'RE SWEATY OR SHIVERING.

The symptoms of a panic attack can look a lot like the flu. But if you don't have a fever and no one else has chattering teeth, it might be your ANS in distress.

6. YOU KNOW THE WORST IS COMING.

While it may sound prophetic or at least bizarre, a sense of impending doom is a very common symptom of panic attacks (and several other conditions). 

7. BREATHING IS DIFFICULT.

The ANS strikes again. In addition to the well-known problems of hyperventilation or shortness of breath, panic attacks can also cause dyspnea, in which a person feels like they can't fill their lungs, and feelings of choking or being smothered.

8. YOU'RE AFRAID OF HAVING A PANIC ATTACK. 

Oddly enough, anxiety about anxiety is itself a symptom of anxiety and panic attacks. Fear of losing control or getting upset can cause people to avoid situations that could be triggering, which can in turn limit their lives. 

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