{"title":"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。","authors":"","doi":"10.1016/j.alcohol.2024.08.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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<sub>0–600 min</sub>): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC<sub>0–600 min</sub>: 453 ± 333 ng/ml × min, <em>P</em> = 0.03) but not Predisposed (AUC<sub>0–600 min</sub>: 556 ± 429 ng/ml × min, <em>P</em> = 0.11).</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":7712,"journal":{"name":"Alcohol","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0741832924001125/pdfft?md5=4c41d86367cd092ec5e9a21468750d4b&pid=1-s2.0-S0741832924001125-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Alcohol-induced fibroblast growth factor 21 secretion is increased in individuals with alcohol use disorder\",\"authors\":\"\",\"doi\":\"10.1016/j.alcohol.2024.08.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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<sub>0–600 min</sub>): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC<sub>0–600 min</sub>: 453 ± 333 ng/ml × min, <em>P</em> = 0.03) but not Predisposed (AUC<sub>0–600 min</sub>: 556 ± 429 ng/ml × min, <em>P</em> = 0.11).</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":7712,\"journal\":{\"name\":\"Alcohol\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0741832924001125/pdfft?md5=4c41d86367cd092ec5e9a21468750d4b&pid=1-s2.0-S0741832924001125-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alcohol\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0741832924001125\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alcohol","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0741832924001125","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Alcohol-induced fibroblast growth factor 21 secretion is increased in individuals with alcohol use disorder
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 (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).
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.
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.
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