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Updated: Mar 15, 2026
Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
Published on: April 16, 2019
Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency
Silvia Sookoian1, Puneet Puri2, Gustavo O Castaño3
1Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires- National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Background And Aims:
Nonalcoholic fatty liver disease (NAFLD) develops from a complex process, which includes changes in the liver methylome. Betaine plays a pivotal role in the regulation of methylogenesis. We performed a two-stage case-control study, which included patients with biopsy-proven NAFLD to explore circulating levels of betaine and its association with the histological spectrum. We also explored the association between a missense rs1805074, p.Ser646Pro variant in DMGDH (dimethylglycine dehydrogenase mitochondrial) and NAFLD severity (n=390).
Results:
In the discovery phase (n=48), betaine levels were associated with the disease severity (P=.0030), including liver inflammation (Spearman R:-0.51, P=.001), ballooning degeneration (R: -0.50, P=.01) and fibrosis (R: -0.54, P=.0008). Betaine levels were significantly decreased in nonalcoholic steatohepatitis (NASH) in comparison with nonalcoholic fatty liver (NAFL). Further replication (n=51) showed that betaine levels were associated with advanced NAFLD (P=.0085), and patients with NASH had a 1.26-fold decrease in betaine levels compared with those with NAFL. The rs1805074 was significantly associated with the disease severity (P=.011).
Conclusion:
NAFLD severity is associated with a state of betaine-insufficiency.
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