Acceleration of liver regeneration by betaine supplementation via enhancement of sulfur‐containing amino acid metabolism

Our earlier work showed that hepatic S‐adenosylmethionine (SAM) level was critically associated with liver regenerative process. In this study we examined the progression of liver regeneration in the rats treated with betaine, a methyl donor that increases the generation of SAM in liver. Male rats received betaine in drinking water from 2 wk prior to 2/3 partial hepatectomy (PHx). Liver growth was more rapid in the rats treated with betaine from 48 h after PHx. Induction of cyclin D1 expression in liver was accelerated, and remained elevated for 24 h. Proliferating cell nuclear antigen expression in liver was significantly greater in the betaine‐treated rats at 24 and 48 h after the surgery. Methionine, SAM, cysteine, glutathione, and taurine were all increased by PHx. The increase in methionine and SAM was intensified significantly in the rats provided with betaine. The surgical treatment elevated putrescine and spermidine, but decreased spermine levels in the remnant livers. Betaine treatment markedly enhanced the elevation of putrescine and spermidine levels. In conclusion, the results suggest that betaine may be useful as a therapeutic liver‐regenerating agent both in the remnant liver and in the transplanted liver. The elevation of hepatic SAM, a metabolic substrate for polyamine synthesis, appears to play an important role in the acceleration of liver regeneration in the rats treated with betaine.