美国德州大学西南医学中心Steven A. Kliewer等研究人员合作发现，FGF21通过激活去甲肾上腺素能神经系统来抵消酒精中毒。该研究于2023年3月7日发表于国际一流学术期刊《细胞—代谢》。

研究人员表明，在小鼠和人类肝脏中被乙醇强烈诱导的激素FGF21能刺激醉酒后的唤醒，而不改变乙醇的分解作用。缺少FGF21的小鼠在接触乙醇后，需要比野生型小鼠花费更长的时间来恢复它们的纠正反射和平衡。相反，药用FGF21可以减少小鼠从乙醇引起的昏迷和共济失调中恢复的时间。FGF21不能抵消氯胺酮、地西泮或戊巴比妥引起的镇静作用，这表明对乙醇有特异性。FGF21通过直接激活调节唤醒和警觉性的蓝斑区去甲肾上腺素能神经元而介导其抗毒作用。这些结果表明，这种FGF21的肝脑途径是为了防止乙醇引起的中毒而演化的，它可能是治疗急性酒精中毒的药用靶标。

据了解，食用发酵水果和花蜜的动物有可能接触到乙醇和醉酒的有害影响。

附：英文原文

Title: FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system

Author: Mihwa Choi, Marc Schneeberger, Wei Fan, Abhijit Bugde, Laurent Gautron, Kevin Vale, Robert E. Hammer, Yuan Zhang, Jeffrey M. Friedman, David J. Mangelsdorf, Steven A. Kliewer

Issue&Volume: 2023/03/07

Abstract: Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, stimulates arousal from intoxication without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediates its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region, which regulates arousal and alertness. These results suggest that this FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning.

DOI: 10.1016/j.cmet.2023.02.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00041-4