Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

Bucher, Simon; Begriche, Karima; Catheline, Daniel; Trak-Smayra, Viviane; Tiaho, François; Coulouarn, Cédric; Pinon, Grégory; Lagadic‐Gossmann, Dominique; Rioux, Vincent; Fromenty, Bernard

doi:10.1007/s00394-019-02017-1

Cited by 12 publications

(5 citation statements)

References 80 publications

(110 reference statements)

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“…This finding was consistent with prior MR studies on the association of alcohol with cardiovascular diseases and NAFLD [39][40][41]. However, in our previous study, we found that low-to-moderate drinking regardless of alcohol type was inversely associated with liver fat content [12], which was also observed in mouse models [42,43]. In the current study, the J-shaped correlation between alcohol use and HCC in participants carrying the CC genotype of PNPLA3 rs738409 was consistent among alcohol types.…”

Section: Discussionsupporting

confidence: 92%

Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis

Liu

Song

Suo

et al. 2022

BMC Med

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Background Heavy drinking was well associated with an increased risk of hepatocellular carcinoma (HCC), whereas the effect of low-to-moderate drinking on HCC remains under debate. Methods Participants from the UK Biobank with detailed information on alcohol use and free of common diseases were included. Daily pure alcohol intake (g/day) was calculated, and the predominant alcoholic beverage type was assigned for each participant. Additive Cox regression model and nonlinear Mendelian randomization (NLMR) analyses were performed to evaluate the association of alcohol intake with HCC. Results Of 329,164 participants (52.3% females, mean [SD] age = 56.7 [8.0] years), 201 incident HCC cases were recorded during the median follow-up of 12.6 years. The best-fitted Cox regression model suggested a J-shaped relationship between daily alcohol intake level and HCC risk. However, NLMR analysis did not detect a nonlinear correlation between alcohol use and HCC (nonlinearity P-value: 0.386). The J-shaped correlation pattern was detected only in subjects who mainly drank wine but not in those who mainly drank beer, spirits, or fortified wine. Moderate wine drinking showed a significant alanine transaminase (ALT)- and aspartate aminotransferase-lowering effect compared to that of the nondrinkers. In low-risk populations of HCC including women, people aged < 60 years, subjects with normal ALT levels, and those carrying non-risk genotypes of PNPLA3 rs738409 and TM6SF2 rs58542926, we observed a J-shaped correlation between alcohol use and HCC; however, a positive dose–response correlation was found in their respective counterparts, even in those predominantly drinking wine. Conclusions Low-to-moderate drinking may be inversely associated with the risk of HCC in low-risk populations, which may be largely driven by wine drinking. However, those in high-risk populations of HCC, such as men and older people, and those with abnormal ALT levels and carry genetic risk variants, should abstain from drinking alcohol. Given the small HCC case number, further validations with larger case numbers are warranted in future works.

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Section: Discussionsupporting

confidence: 92%

Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis

Liu

Song

Suo

et al. 2022

BMC Med

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“…Next, we determined whether oxidative stress was implicated in the immune response gene expression profile as suggested by the increase in macrophage markers by FFC and FFC-EtOH ( Fig 2B ). In a genetic model of obesity, EtOH upregulated oxidative stress markers, such as heme oxygenase 1 ( Hmox1 ) [ 33 ], while EtOH has also been found to downregulate oxidative stress in HFD-fed mice [ 34 ]. In the present model, compared with Chow, FFC-EtOH and FFC significantly upregulated hepatic gene expression of Hmox1 (P = 0.004 and P = 0.0002, respectively), but there was no significant difference in Cyp2e1 gene expression between the diet groups.…”

Section: Resultsmentioning

confidence: 99%

Concomitant western diet and chronic-binge alcohol dysregulate hepatic metabolism

et al. 2023

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Background and aims There is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) with regards to risk factors and disease progression. However, the mechanism by which fatty liver disease arises from concomitant obesity and overconsumption of alcohol (syndrome of metabolic and alcohol-associated fatty liver disease; SMAFLD), is not fully understood. Methods Male C57BL6/J mice were fed chow diet (Chow) or high-fructose, high-fat, high-cholesterol diet (FFC) for 4 weeks, then administered either saline or ethanol (EtOH, 5% in drinking water) for another 12 weeks. The EtOH treatment also consisted of a weekly 2.5 g EtOH/kg body weight gavage. Markers for lipid regulation, oxidative stress, inflammation, and fibrosis were measured by RT-qPCR, RNA-seq, Western blot, and metabolomics. Results Combined FFC-EtOH induced more body weight gain, glucose intolerance, steatosis, and hepatomegaly compared to Chow, EtOH, or FFC. Glucose intolerance by FFC-EtOH was associated with decreased hepatic protein kinase B (AKT) protein expression and increased gluconeogenic gene expression. FFC-EtOH increased hepatic triglyceride and ceramide levels, plasma leptin levels, hepatic Perilipin 2 protein expression, and decreased lipolytic gene expression. FFC and FFC-EtOH also increased AMP-activated protein kinase (AMPK) activation. Finally, FFC-EtOH enriched the hepatic transcriptome for genes involved in immune response and lipid metabolism. Conclusions In our model of early SMAFLD, we observed that the combination of an obesogenic diet and alcohol caused more weight gain, promoted glucose intolerance, and contributed to steatosis by dysregulating leptin/AMPK signaling. Our model demonstrates that the combination of an obesogenic diet with a chronic-binge pattern alcohol intake is worse than either insult alone.

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“…An experimental study on mice fed with a high-fat diet and ethanol-added water [ 48 ] suggested that alcohol induced the generation of non-toxic lipid species (including triglycerides enriched in mono-unsaturated fatty acids), reduced the expression of pro-inflammatory and pro-fibrotic genes, and restored mitochondrial function. A downregulation of several pro-apoptotic genes with a concomitant increased expression of anti-apoptotic genes was also detected.…”

Section: Nafldmentioning

confidence: 99%

Effect of Low-Dose Alcohol Consumption on Chronic Liver Disease

Andaloro,

Mancuso,

Miele

et al. 2024

Nutrients

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Although alcohol is one of the most important etiologic agents in the development of chronic liver disease worldwide, also recognized as a promoter of carcinogenesis, several studies have shown a beneficial effect of moderate consumption in terms of reduced cardiovascular morbidity and mortality. Whether this benefit is also present in patients with liver disease due to other causes (viral, metabolic, and others) is still debated. Although there is no clear evidence emerging from guidelines and scientific literature, total abstention from drinking is usually prescribed in clinical practice. In this review, we highlight the results of the most recent evidence on this controversial topic, in order to understand the effect of mild alcohol use in this category of individuals. The quantification of alcohol intake, the composition of the tested populations, and the discrepancy between different works in relation to the outcomes represent important limitations emerging from the scientific literature. In patients with NAFLD, a beneficial effect is demonstrated only in a few works. Even if there is limited evidence in patients affected by chronic viral hepatitis, a clear deleterious effect of drinking in determining disease progression in a dose-dependent manner emerges. Poor data are available about more uncommon pathologies such as hemochromatosis. Overall, based on available data, it is not possible to establish a safe threshold for alcohol intake in patients with liver disease.

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Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

Abstract: Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet. Possible role of higher formation of triglycerides enriched in monounsaturated fatty acids

Cited by 12 publications

References 80 publications

Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis

Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis

Concomitant western diet and chronic-binge alcohol dysregulate hepatic metabolism

Effect of Low-Dose Alcohol Consumption on Chronic Liver Disease

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