KAT8, lysine acetyltransferase 8, is required for adipocyte differentiation in vitro

Abstract

KAT8 is a lysine acetyltransferase (KAT) that plays a role in a variety of cellular functions ranging from DNA damage repair to apoptosis. The role of KAT8 in adipocyte development and function has not been studied. Notably, a large genome-wide association study identified KAT8 as part of a novel locus that significantly contributed to body mass index and other metabolic phenotypes. Hence, we examined the expression and regulation of KAT8 during adipocyte development. KAT8 mRNA and protein levels were examined over a time course of adipocyte development, and KAT8 was found to be present in both the cytosol and nucleus of 3T3-L1 adipocytes. Although KAT8 expression was not highly regulated by adipogenesis, its expression was required for the adipogenesis of 3T3-L1 cells. Loss of KAT8 expression in preadipocytes inhibited their ability to differentiate as judged by both lipid accumulation and adipocyte marker gene expression. However, if KAT8 was knocked down after clonal expansion, its absence did not inhibit adipocyte differentiation. Also, loss of KAT8 in adipocytes did not impact lipid accumulation or the expression of adiponectin or other fat markers. Although our data demonstrate that KAT8 is required for adipocyte differentiation, further studies are necessary to determine the functions and regulation of KAT8 in adipose tissue.

Keywords: Adipocyte; Adipogenesis; Epigenetic; KAT8.