Abstract：
BACKGROUND: Alcohol use disorder (AUD) affects 5% of the global population. Despite its high prevalence, the pathophysiology of AUD remains enigmatic, hindering the development of novel therapeutics. Interestingly, the liver hormone fibroblast growth factor 21 (FGF21), which is currently in late-stage clinical trials for the treatment of non-alcoholic steatohepatitis, has been implicated by recent genome-wide association studies as a regulator of alcohol consumption.
METHODS: This study aimed to evaluate plasma responses of FGF21 to an alcohol challenge in three groups: 15 males with AUD, 15 healthy males with a father with AUD (Predisposed) and 15 healthy males without any predisposition to AUD (Controls). All participants were investigated after an overnight fast. Assessments, including blood sampling and visual analog scale-assessed desire for alcohol intake, were performed before and for 10 hours after ingesting 0.5 g alcohol per kg body weight over 10 minutes.
RESULTS: The three groups were age and body-mass index-matched and had normal plasma concentrations of transaminases and FibroScan®-assessed elastography. Baseline FGF21 concentrations did not differ between groups, but individuals with AUD exhibited greater FGF21 responses to alcohol (area under the curve (AUC0-600 min): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC0-600 min: 453 ± 333 ng/ml × min, P = 0.03) but not Predisposed (AUC0-600 min: 556 ± 429 ng/ml × min, P = 0.11).
CONCLUSIONS: In conclusion, we demonstrate greater alcohol-induced FGF21 responses in individuals with AUD compared to healthy individuals without paternal predisposition to AUD, suggesting a role for FGF21 in AUD pathophysiology.
METHODS: This study aimed to evaluate plasma responses of FGF21 to an alcohol challenge in three groups: 15 males with AUD, 15 healthy males with a father with AUD (Predisposed) and 15 healthy males without any predisposition to AUD (Controls). All participants were investigated after an overnight fast. Assessments, including blood sampling and visual analog scale-assessed desire for alcohol intake, were performed before and for 10 hours after ingesting 0.5 g alcohol per kg body weight over 10 minutes.
RESULTS: The three groups were age and body-mass index-matched and had normal plasma concentrations of transaminases and FibroScan®-assessed elastography. Baseline FGF21 concentrations did not differ between groups, but individuals with AUD exhibited greater FGF21 responses to alcohol (area under the curve (AUC0-600 min): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC0-600 min: 453 ± 333 ng/ml × min, P = 0.03) but not Predisposed (AUC0-600 min: 556 ± 429 ng/ml × min, P = 0.11).
CONCLUSIONS: In conclusion, we demonstrate greater alcohol-induced FGF21 responses in individuals with AUD compared to healthy individuals without paternal predisposition to AUD, suggesting a role for FGF21 in AUD pathophysiology.
摘要：
背景：酒精使用障碍（AUD）影响全球5%的人口。尽管流行率很高,AUD的病理生理学仍然是神秘的，阻碍了新疗法的发展。有趣的是,肝脏激素成纤维细胞生长因子21（FGF21），目前正在进行治疗非酒精性脂肪性肝炎的后期临床试验，最近的全基因组关联研究涉及酒精消费的调节因素。
方法：本研究旨在评估三组FGF21对酒精攻击的血浆反应：15名男性，AUD，15名健康男性，父亲有AUD（易感），15名健康男性没有任何AUD倾向（对照）。所有参与者在过夜禁食后进行了调查。评估，包括血液采样和视觉模拟量表评估对酒精摄入的渴望，在10分钟内每公斤体重摄入0.5g酒精之前和之后进行10小时。
结果：三组的年龄和体重指数匹配，血浆转氨酶和FibroScan®评估弹性成像的浓度正常。基线FGF21浓度在组间没有差异，但与对照组（AUC0-600分钟：453±333ng/ml×min，曲线下面积（AUC0-600分钟）：954±665ng/ml×min（平均值（标准偏差）））相比，具有AUD的个体对酒精表现出更大的FGF21反应，P=0.03），但不倾向于（AUC0-600min：556±429ng/ml×min，P=0.11）。
结论：结论：我们证明，与没有父亲对AUD易感性的健康个体相比，在AUD个体中酒精诱导的FGF21反应更大，提示FGF21在AUD病理生理学中的作用。
方法：本研究旨在评估三组FGF21对酒精攻击的血浆反应：15名男性，AUD，15名健康男性，父亲有AUD（易感），15名健康男性没有任何AUD倾向（对照）。所有参与者在过夜禁食后进行了调查。评估，包括血液采样和视觉模拟量表评估对酒精摄入的渴望，在10分钟内每公斤体重摄入0.5g酒精之前和之后进行10小时。
结果：三组的年龄和体重指数匹配，血浆转氨酶和FibroScan®评估弹性成像的浓度正常。基线FGF21浓度在组间没有差异，但与对照组（AUC0-600分钟：453±333ng/ml×min，曲线下面积（AUC0-600分钟）：954±665ng/ml×min（平均值（标准偏差）））相比，具有AUD的个体对酒精表现出更大的FGF21反应，P=0.03），但不倾向于（AUC0-600min：556±429ng/ml×min，P=0.11）。
结论：结论：我们证明，与没有父亲对AUD易感性的健康个体相比，在AUD个体中酒精诱导的FGF21反应更大，提示FGF21在AUD病理生理学中的作用。
