Alcohol-induced fibroblast growth factor 21 secretion is increased in individuals with alcohol use disorder

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY Alcohol Pub Date : 2024-08-05 DOI:10.1016/j.alcohol.2024.08.001

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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 h after ingesting 0.5 g alcohol per kg body weight over 10 min.

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 (AUC_0–600 min): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC_0–600 min: 453 ± 333 ng/ml × min, P = 0.03) but not Predisposed (AUC_0–600 min: 556 ± 429 ng/ml × min, P = 0.11).

Conclusion

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.

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酒精诱导的成纤维细胞生长因子 21 在酒精使用障碍患者中分泌增加。

背景：酒精使用障碍（AUD）影响着全球 5% 的人口。尽管发病率很高，但 AUD 的病理生理学仍是一个谜，阻碍了新型疗法的开发。有趣的是，肝脏激素成纤维细胞生长因子 21 (FGF21)目前正处于治疗非酒精性脂肪性肝炎的后期临床试验阶段，最近的全基因组关联研究表明它是酒精消费的调节因子：本研究旨在评估三组人血浆中 FGF21 对酒精挑战的反应：15 名患有 AUD 的男性、15 名父亲患有 AUD 的健康男性（易患者）和 15 名没有任何 AUD 易患者的健康男性（对照组）。所有参与者均在一夜禁食后接受调查。在每公斤体重 10 分钟内摄入 0.5 克酒精之前和之后的 10 小时内进行评估，包括血液采样和视觉模拟量表评估酒精摄入欲望：结果：三组患者的年龄和体重指数相匹配，血浆中转氨酶浓度和纤维扫描弹性成像均正常。各组之间的 FGF21 基线浓度没有差异，但患有 AUD 的个体对酒精的 FGF21 反应更大（曲线下面积 (AUC0-600 min)：954 ± 665 纳克/分钟）：与对照组（AUC0-600 min：453 ± 333 ng/ml × min，P = 0.03）相比，AUD 患者对酒精的 FGF21 反应更大（曲线下面积 (AUC0-600 min)：954 ± 665 ng/ml × min（平均值（标准偏差）），而易感人群（AUC0-600 min：556 ± 429 ng/ml × min，P = 0.11）：总之，我们发现，与没有AUD父系易感性的健康人相比，AUD患者的酒精诱导FGF21反应更大，这表明FGF21在AUD病理生理学中发挥作用。

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来源期刊

Alcohol 医学-毒理学

CiteScore

4.60

自引率

4.30%

发文量

审稿时长

15.6 weeks

期刊介绍： Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.