Elucidating Metabolic and Epigenetic Mechanisms that Regulate Liver Regeneration

The regenerative capability of the liver is essential for recovery from all hepatic injuries. Although long studied, the signals that regulate such regeneration require further elucidation if knowledge about regenerative mechanisms is to be translated into improved clinical therapy. Alterations in metabolism have been the focus of recent experimental investigations as a possible source of essential signals that control liver regeneration. Although the specific mechanisms linking metabolism and regeneration remain unknown, specific growth factors, secondary messengers, and transcription factors have been suggested by published analyses. Epigenetic mechanisms are also emerging as potential intermediaries between hepatic insufficiency-induced changes in metabolism and regenerative hepatocellular proliferation. This article reviews the recent literature relevant to these considerations, with particular emphasis on contemporary data that link metabolic and epigenetic signals to the regulation of liver regulation. The relevance of metabolic–epigenetic regulation of experimental hepatic regeneration with respect to human liver diseases is also briefly considered.