ArticleBritish journal of pharmacology2014
Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Hepatocyte-Specific Deletion of Betaine-Homocysteine Methyltransferase Disrupts Methionine Metabolism and Promotes the Spontaneous Development of Hepatic Steatosis.Biomolecules · 2026Article
- Brown adipose tissue inactivation exacerbates alcohol-induced liver steatosis, inflammation, and fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Lipid Droplet Dynamics in Alcoholic Steatohepatitis.The American journal of pathology · 2026Review
- Comprehensive Analysis of Differentially Expressed Profiles of mRNA 5-Methylcytosine Modification in Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2025Article
- Recent Advances in Betaine: Extraction, Identification, and Bioactive Functions in Human Health.Food science & nutrition · 2025Review
- Betaine regulates the gut-liver axis: a therapeutic approach for chronic liver diseases.Frontiers in nutrition · 2025Review
- Exercise-mimicking effects of betaine in chronic disease prevention and management.Frontiers in nutrition · 2025Review
- Targeting lipid droplets and lipid droplet-associated proteins: a new perspective on natural compounds against metabolic diseases.Chinese medicine · 2024Review
- Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.Signal transduction and targeted therapy · 2024Article
- Alcohol, White Adipose Tissue, and Brown Adipose Tissue: Mechanistic Links to Lipogenesis and Lipolysis.Nutrients · 2023Review
- The role of hypoxia-inducible factor 1α in hepatic lipid metabolism.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors.International journal of molecular sciences · 2022Article
- Alcoholic fatty liver is blunted by rFGF21 administration in mice lacking adipose FGFR1: The role of FGF21 in PPARα-mediated regulation of adipose tissue mass.Biochemical and biophysical research communications · 2022Article
- Alcohol: basic and translational research; 15th annual Charles Lieber &1st Samuel French satellite symposium.Experimental and molecular pathology · 2022Review
- Betaine in ameliorating alcohol-induced hepatic steatosis.European journal of nutrition · 2022Review
- Elevated S-adenosylhomocysteine induces adipocyte dysfunction to promote alcohol-associated liver steatosis.Scientific reports · 2021Article
- Beneficial Effects of Betaine: A Comprehensive Review.Biology · 2021Review
- ER stress-induced upregulation of NNMT contributes to alcohol-related fatty liver development.Journal of hepatology · 2020Article
- Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner.Redox biology · 2020Article
- Role of betaine in inhibiting the induction of RNA Pol III gene transcription and cell growth caused by alcohol.Chemico-biological interactions · 2020Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeOveractive lipolysis in adipose tissue contributes to the pathogenesis of alcoholic liver disease (ALD); however, the mechanisms involved have not been elucidated. We previously reported that chronic alcohol consumption produces a hypomethylation state in adipose tissue. In this study we investigated the role of hypomethylation in adipose tissue in alcohol-induced lipolysis and whether its correction contributes to the well-established hepatoprotective effect of betaine in ALD. EXPERIMENTAL APPROACH: Male C57BL/6 mice were divided into four groups and started on one of four treatments for 5 weeks: isocaloric pair-fed (PF), alcohol-fed (AF), PF supplemented with betaine (BT/AF) and AF supplemented with betaine (BT/AF). Betaine, 0.5% (w v(-1) ), was added to the liquid diet. Both primary adipocytes and mature 3T3-L1 adipocytes were exposed to demethylation reagents and their lipolytic responses determined. KEY
resultsBetaine alleviated alcohol-induced pathological changes in the liver and rectified the impaired methylation status in adipose tissue, concomitant with attenuating lipolysis. In adipocytes, inducing hypomethylation activated lipolysis through a mechanism involving suppression of protein phosphatase 2A (PP2A), due to hypomethylation of its catalytic subunit, leading to increased activation of hormone-sensitive lipase (HSL). In line with in vitro observations, reduced PP2A catalytic subunit methylation and activity, and enhanced HSL activation, were observed in adipose tissue of alcohol-fed mice. Betaine attenuated this alcohol-induced PP2A suppression and HSL activation. CONCLUSIONS AND IMPLICATIONS: In adipose tissue, a hypomethylation state contributes to its alcohol-induced dysfunction and an improvement in its function may contribute to the hepatoprotective effects of betaine in ALD.
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