ReferenceID 3397
Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease
Br J Pharmacol
BACKGROUND AND PURPOSE: Overactive 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 chro
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Record Fields
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- Reference Id
- 3397
- Evidence Id
- 19987
- Core Evidence Id
- 19987
- Source Reference Id
- 81
- Herb2 Reference Id
- HBREF000220
- Subject Paper Key
- HBIN018163_24819676
- Pubmed Id
- 24819676
- Doi
- 10.1111/bph.12765
- Paper Title
- Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease
- Paper Abstract
- BACKGROUND AND PURPOSE: Overactive 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 RESULTS: Betaine 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.
- Journal
- Br J Pharmacol
- Publish Year
- 2014
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Alcoholic Liver Disease
- Paper Title Cn
- Paper Title En
- Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease
- Bilingual Status
- semi_complete