喜欢不醉不休的人，大都有属于自己的醒酒妙招：洗个冰水澡或喝点蜂蜜水。而对于美国得克萨斯州一个实验室的小鼠来说，来上一针就能迅速清醒。
一项新研究表明，注射成纤维细胞生长因子 21（fibroblast growth factor 21，FGF21），一种调节代谢的激素后，醉酒小鼠恢复清醒并开始跑动的时间是自然醒酒小鼠的一半。更重要的是，相比与 FGF21 水平正常的小鼠，缺乏这种激素的小鼠会喝下更多的酒、恢复清醒的时间也更长。研究结果发表在《细胞代谢》（Cell Metabolism）杂志上。
史蒂夫·克利韦尔（Steve Kliewer）：“我们想知道 FGF21 对乙醇的急性反应有什么作用。” 克利韦尔是美国得克萨斯大学（University of Texas）西南医学中心（Southwestern Medical Center）的分子生物学教授，他和得克萨斯大学药理学系教授兼系主任大卫·“达沃”·曼格尔斯多夫（David "Davo" Mangelsdorf）共同经营一个实验室，后者同时也是美国霍华德·休斯医学研究所（Howard Hughes Medical Institute）的研究员。
美国路易斯维尔大学（University of Louisville）的一个研究团队发现，乙醇会导致小鼠体内的 FGF21 水平飙升。而后，克利韦尔的研究团队和其他研究团队发现，在人类身上也是如此。他们与奥地利的一位研究人员合作，在一群年轻冰球运动员身上进行了测试。
30 分钟里几杯伏特加下肚，而后 1~4 小时内，冰球运动员血液中的 FGF21 水平便飙升，且一直保持在很高的水平，比其他任何能诱导人体内 FGF21 水平上升的物质都要高。克利韦尔表示这是从未在人体中见过的数据，他们也因此对乙醇诱导下的 FGF21 产生了兴趣。
作为分子生物学家，他们做的第一件事就是用 FGF21 基因敲除小鼠进行实验，让这些小鼠日饮亡何，喝到基本丧失能力为止。基因敲除小鼠和没有进行基因编辑的对照组小鼠都烂醉如泥，但基因敲除小鼠恢复意识的时间是对照组的两倍。
当你喝酒时，你的肝脏会促进 FGF21 的分泌，这种激素也能控制身体对进食或饥饿的反应。事实证明，FGF21 不仅能让你从酩酊大醉中清醒过来，它还会……[查看全文]
From Stupor to Sober with One (Hormone) Shot
Karen Hopkin: This is Scientific American's Science, Quickly. I'm Karen Hopkin.We all have our tricks for sobering up after a night of drunken revelry: maybe a pot of black coffee or an ice-cold shower. But for mice in a certain lab in Texas, all it takes is a shot. No, not more alcohol—it's an injection of a hormone called fibroblast growth factor 21, or FGF21.What's more, mice lacking FGF21 drink more—and take longer to recover from alcohol's effects—than their hormonally competent counterparts. The findings appear in the journal Cell Metabolism.Steve Kliewer: The genesis of this particular project was the finding from several laboratories that this particular hormone that we work on, FGF21, is induced dramatically by ethanol. We wanted to know: "What does FGF21 do acutely in terms of ethanol response to ethanol?"Hopkin: Steve Kliewer is a professor of molecular biology at the University of Texas Southwestern Medical Center.Kliewer: I run a lab jointly with this fellow.David "Davo" Mangelsdorf: And this fellow is David Mangelsdorf. I am a professor and chair of the Department of Pharmacology at U.T. Southwestern and also an investigator of the Howard Hughes Medical Institute.
Hopkin: The two actually met as postdocs at the Salk Institute in San Diego. But after they went their separate ways, they found they often gravitated to the same sorts of questions.Kliewer: And we ended up publishing a couple of big papers back-to-back during that period... It was a pretty intense competition, right?
Mangelsdorf: Whenever we had a discovery, I was always worried, rightfully so, that Steve's group also had the same discoveries.Hopkin: So when Steve joined the faculty at U.T. Southwestern...
Mangelsdorf: It just made sense to start working together...
Hopkin: And not just to bask in the academic kumbaya vibes.
Mangelsdorf: I often say that the best way to get rid of your competition is to make them your collaborator.
Kliewer: Asking big questions requires big resources, and doing this makes things more efficient. So I think it just makes sense.
Mengelsdorf: It makes it more fun, to be honest, [to] have somebody that you can throw your ideas off of and not be worried that they're gonna steal them or something, right?
Hopkin: Okay, where were we? Right, the drunken mice. So a team at the University of Louisville had shown that, in mice, ethanol causes FGF21 levels to soar.
Kliewer: And then our group and other groups showed that this was true not just in mice but also in humans.
Hopkin: They teamed up with a researcher in Austria who gathered a gaggle of young hockey players.
Mangelsdorf: He recruited them to take some shots of vodka over a 30-minute period and monitor their blood levels of FGF21. And he showed that after a couple of shots of vodka, it spiked within just an hour up to four hours. It just stayed very high, higher than anything else that has ever been seen for inducing FGF21 in a human.
Kliewer: So when he originally showed us this data, we didn't believe him. At least I didn't believe him. The levels were so high, and nothing like that had been seen in humans. And so that was one of those aha! moments that really grabbed our attention and got us to pivot to really think about FGF21 in the context of ethanol and to focus on that aspect of this hormone.
Hopkin: So as card-carrying molecular biologists, the first thing they did was take some mice and disable the gene for FGF21.
Kliewer: We refer to these as FGF21 knockout mice.
Hopkin: And they gave the knockout mice, as well as genetically unaltered control mice, a binge dose of ethanol.
Mangelsdorf: It would be going to the bar and drinking yourself silly until you are essentially incapacitated.
Hopkin: At that point, the knockout mice and the control mice were all, um, knocked out.Kliewer: But what we noticed–what was really remarkable and obvious–was that the knockout mice took twice as long to recover consciousness as the control mice.Hopkin: So when you drink, your liver boosts production of FGF21, a hormone that also governs the body's response to diet or starvation. That hormone, it turns out, not only helps bring you out of your drunken stupor...
Choi, M., Schneeberger, M., Fan, W., Bugde, A., Gautron, L., Vale, K., Hammer, R.E., Zhang, Y., Friedman, J.M., Mangelsdorf, D.J. and Kliewer, S.A. (2023). FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system. Cell Metabolism, [online] 35(3), pp.429-437.e5.
DOI: 10.1016/j.cmet.2023.02.005
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