Abstract
The composition of the liver changes dramatically with age. Hepatocytes in young individuals are relatively small and uniform in size. In contrast, adult hepatocytes vary considerably in cell and nuclear size, number of nuclei per cell and DNA content per nucleus (1, 2). Many of these striking age-associated morphological changes are attributed to hepatic polyploidy, a numerical change in the entire complement of chromosomes. Polyploid hepatocytes were recognized over a century ago, but it is unclear whether these cells play a specialized role in liver homeostasis, regeneration or disease. Despite our limited understanding of the physiological role of polyploid hepatocytes, nearly a dozen genes have been implicated in the regulation of polyploidy (2). Notably, Chantal Desdouets’ group previously demonstrated a critical role for insulin in the generation of binucleate polyploid hepatocytes in rats (3). Motivated by these early findings, Gentric, Celton-Morizur, Desdouets and colleagues rationalized that liver diseases frequently associated with dysregulated insulin signaling could have an abnormal ploidy spectrum. Indeed, in recent work the authors identified a connection between abnormal hepatic polyploidy and nonalcoholic fatty liver disease (NAFLD)