Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/- mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/- mice was not enhanced. Instead, the Tsc2+/- livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation. (C) 2013 Elsevier Inc. All rights reserved.