Circulating NAMPT (PBEF/visfatin) has pleiotropic functions and is secreted from adipocytes. Since it is doubtful whether serum levels can be explained by secretion from adipocytes alone, we asked whether hepatocytes are also able to liberate NAMPT. Using HepG2 cells and primary rat and human hepatocytes, release of NAMPT into the cell Culture Supernatant was found to Occur Constitutively in a time-dependent manner. In primary human hepatocytes, secretion within 24 h was far higher than the cellular content, but was neither influenced by inhibitors of secretion nor by glucose. insulin or TNF alpha. As determined by size exclusion chromatography. HepG2 lysates and supernatants primarily contained the dimeric form of NAMPT which exhibited similar in vitro specific enzymatic activity In primary human hepatocytes, secreted NAMPT was less active Our results demonstrate that human hepatocytes are a potential Source of circulating NAMPT (C) 2009 Elsevier Inc. All rights reserved.