The fructose-dependent acceleration of ethanol metabolism

Villalobos-García, Daniel; Ayhllon-Osorio, Carlos Alberto; Hernández‐Muñoz, Rolando

doi:10.1016/j.bcp.2021.114498

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…Fructose also influences the intestinal barrier by regulating ethanol metabolism ( Bradford et al, 1991 ; Uzuegbu and Onyesom, 2009 ; Villalobos-García et al, 2021 ). In alcohol-fed mice that lack alcohol dehydrogenase (ADH), fructose administration decreases the rates of ethanol metabolism by about 60% via diminishing H 2 O 2 generation ( Bradford et al, 1991 ).…”

Section: Dietary Fructose and Intestinal Environmentmentioning

confidence: 99%

The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

Yu¹,

Li²,

Ji³

et al. 2021

Front. Pharmacol.

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Fructose, especially industrial fructose (sucrose and high fructose corn syrup) is commonly used in all kinds of beverages and processed foods. Liver is the primary organ for fructose metabolism, recent studies suggest that excessive fructose intake is a driving force in non-alcoholic fatty liver disease (NAFLD). Dietary fructose metabolism begins at the intestine, along with its metabolites, may influence gut barrier and microbiota community, and contribute to increased nutrient absorption and lipogenic substrates overflow to the liver. Overwhelming fructose and the gut microbiota-derived fructose metabolites (e.g., acetate, butyric acid, butyrate and propionate) trigger the de novo lipogenesis in the liver, and result in lipid accumulation and hepatic steatosis. Fructose also reprograms the metabolic phenotype of liver cells (hepatocytes, macrophages, NK cells, etc.), and induces the occurrence of inflammation in the liver. Besides, there is endogenous fructose production that expands the fructose pool. Considering the close association of fructose metabolism and NAFLD, the drug development that focuses on blocking the absorption and metabolism of fructose might be promising strategies for NAFLD. Here we provide a systematic discussion of the underlying mechanisms of dietary fructose in contributing to the development and progression of NAFLD, and suggest the possible targets to prevent the pathogenetic process.

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Section: Dietary Fructose and Intestinal Environmentmentioning

confidence: 99%

The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

Yu¹,

Li²,

Ji³

et al. 2021

Front. Pharmacol.

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“…It could also be shown that both glucose and fructose accelerate ethanol metabolism, whereas potential mechanisms remain controversial 45–47 . A recent study indicates that the effect of fructose on ethanol elimination is mediated by an increased NADH consumption of hepatocytes after fructose administration 48 . In the present analysis, the composition of administered meals is known only for the study performed by Ammon et al, 24 where all subjects received chicken with rice (27 g fat, 5 g protein, 57 g carbohydrates, 381 kcal) 30 minutes before ethanol administration.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics as a Tool to Reevaluate the Complex Disposition of Ethanol in the Fed and Fasted States

Büsker

Jones

Hahn

et al. 2023

The Journal of Clinical Pharma

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The pharmacokinetics (PK) of ethanol are important in pharmacology and therapeutics because of potential drug‐alcohol interactions as well as in forensic science when alcohol‐related crimes are investigated. The PK of ethanol have been extensively studied since the 1930s, although some issues remain unresolved, such as the significance of first‐pass metabolism, whether zero‐order kinetics apply, and the effects of food on bioavailability. We took advantage of nonlinear mixed‐effects modeling to describe blood‐alcohol concentration (BAC) profiles derived from 3 published clinical studies involving oral, intraduodenal, and intravenous administration of ethanol with and without food. The overall data set included 1510 BACs derived from 72 healthy subjects (60 men, 12 women) aged between 20 and 60 years. Two‐compartment models with first‐order absorption and Michaelis‐Menten elimination kinetics adequately described the BAC profiles. Food intake had 2 separate effects: It reduced the absorption rate constant and accelerated the maximum elimination rate. Estimates of the maximum elimination rate (fasted) and the food effect (as a factor) were 6.31 g/h (95%CI, 6.04‐6.59 g/h) and 1.39‐fold (95%CI, 1.33‐1.46‐fold), respectively. Simulations showed that the area under the BAC‐time curve (AUC) was smaller with lower input rate of ethanol, irrespective of any first‐pass metabolism. The AUC from time 0 to 10 hours for a 75‐kg subject was 2.34 g • h/L (fed) and 3.83 g • h/L (fasted) after an oral dose of 45 g ethanol. This difference was mainly attributable to the food effect on ethanol elimination and depended less on the absorption rate. Our new approach to explain the complex human PK of ethanol may help when BAC predictions are made in clinical pharmacology and forensic medicine.

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“…4-Methylpyrazole is a competitive inhibitor of alcohol dehydrogenase [46][47][48]. In a previous study on the transcriptome of B. xylophilus treated with 4-Methylpyrazole, an upregulated gene BxCAD-1 coding cinnamyl alcohol dehydrogenase was identified [49].…”

Section: Introductionmentioning

confidence: 99%

Cinnamyl Alcohol Dehydrogenase Gene Regulates Bursaphelenchus xylophilus Reproduction and Development

Dong,

Guo,

Deng

et al. 2023

Forests

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Pine wilt disease (PWD) caused by the pine wood nematode (PWN), Bursaphelenchus xylophilus, is a globally distributed destructive disease of pine forest. To study the PWD pathogenic mechanism, the cinnamyl alcohol dehydrogenase gene (BxCAD-1) from B. xylophilus was selected. The BxCAD-1 gene was amplified by PCR from the cDNA library of B. xylophilus and cloned into the expression vector pET-15b to construct the recombinant vector pET-15b-BxCAD-1. The recombinant cinnamyl alcohol dehydrogenase protein was purified by Ni-NTA affinity chromatography from Escherichia coli BL21 (DE3) harboring pET-15b-BxCAD-1 induced by IPTG. The effects of pH, temperature, metal ions and substrates on the activity of BxCAD-1 were determined, showing the highest catalytic activity at pH 8.0 and 40 °C with cinnamyl alcohol as substrate and Zn2+ as an activator. To elucidate the functions of BxCAD-1 in B. xylophilus, the expression of the gene was down-regulated by RNA interference. Results showed that the movement, feeding, reproduction, spawning rate, hatching rate, lifespan, infectivity and sensitivity to ethanol decreased compared with negative controls. RNA interference also affected the development of B. xylophilus from the larval stage to the adult stage. In situ hybridization showed that the gene was expressed in the digestive tract of male and female adults. This study revealed a promising target for PWD control.

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The fructose-dependent acceleration of ethanol metabolism

Cited by 4 publications

References 46 publications

The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease

Population Pharmacokinetics as a Tool to Reevaluate the Complex Disposition of Ethanol in the Fed and Fasted States

Cinnamyl Alcohol Dehydrogenase Gene Regulates Bursaphelenchus xylophilus Reproduction and Development

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