This study highlights a unique proteomic response to acute alcohol ingestion and supports further exploration of FGF21 mimetics as potential treatments for alcohol-related disorders.
Abstract
Background The effects of acute alcohol intoxication on the human plasma proteome are still largely unexplored. Gaining insights into this relationship could identify factors that are influenced by and influence alcohol consumption. Fibroblast Growth Factor 21 (FGF21), a hormone produced by the liver and associated with alcohol preferences, is currently undergoing Phase 2 clinical trials for metabolic dysfunction and alcohol-related liver disease. We hypothesized that FGF21 is a key endocrine responsive hormone to alcohol in humans. Methods In a post hoc analysis, we evaluated the effects of five standard units of alcoholic beverages on the plasma proteome in 12 healthy Caucasian men. Participants, fasting for 10 hours, received 0.7 g of alcohol per kg of body weight via gastric infusion, with blood samples collected before and after consumption. Results The proteomic response to this level of alcohol intoxication was highly specific. Of 1,462 proteins measured, only 11 changed significantly and FGF21 exhibited by far the largest increase (10.5-fold). Conclusion This study highlights a unique proteomic response to acute alcohol ingestion and supports further exploration of FGF21 mimetics as potential treatments for alcohol-related disorders.
Objective Chronic alcohol consumption is one of the leading causes of dilated cardiomyopathy. Alcohol-associated cardiomyopathy (ACM) is characterized by impaired cardiac function and ventricular dilation in individuals with a history of long-term alcohol consumption. Alcohol exerts adverse effects on the myocardium vi...
Wei-Lun Ai, Carol A. Casey, K. Rasineni et al.· Frontiers in Cardiovascular...· 0 citations
Genome-wide association studies of alcohol use disorder (AUD) have identified >100 loci, yet the functional impact and the downstream molecular mechanisms are not well understood. As functional effectors of genes, proteins provide direct insight into disease mechanisms. However, most proteomic alterations in postmortem...
Xin-Di Li, Andrew J. Boreland, Arpana Agrawal et al.· bioRxiv· 0 citations
Alcohol metabolism is a multi-step biochemical process driven primarily by hepatic oxidation of ethanol to acetaldehyde and then to acetate. Although this pathway protects the body from prolonged ethanol exposure, transient acetaldehyde accumulation generates substantial toxicity, and chronic alcohol intake activates a...
Evgeny Pechkovsky, B. Kershengoltz, Valentin Vlassov et al.· Frontiers in Toxicology· 0 citations
Background/Objective: Prolonged ethanol use can induce behavioral and physiological alterations and impair the liver’s capacity to metabolize ethanol, leading to hepatocyte injury. The spectrum of this disease ranges from fat accumulation to severe liver damage, including alcohol-related hepatitis and cirrhosis. MC-100...
A. Alotaibi, K. K. Bhowmik, Virender Kumar et al.· Biomedicines· 0 citations
Background Alcoholic liver disease (ALD) is a major global health burden with limited therapeutic options. Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in alcohol metabolism, and ALDH2 deficiency exacerbates alcohol-induced hepatic injury. Aim This study aimed to identify and validate natural ALDH2 activators...
Yuan Lu, Zi-Bin Li, Pan Gao et al.· Frontiers in Nutrition· 0 citations
BACKGROUND & AIMS
Serum alanine aminotransferase (ALT) is commonly used to detect hepatocellular injury. However, genetic and metabolic factors may modulate ALT levels. We focused on the potential impact of an in-activating mutation in aldehyde dehydrogenase 2 (ALDH2*2, rs671) polymorphism, prevalent among East Asians,...
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.