A Novel Mechanism for Hepatic Lipid Accumulation: A Physiological Role for Hepatic PPARγ-fsp27 Signal

Abstract

Fat-speciˆc protein 27 (fsp27) was originally isolated by screening for genes speciˆcally expressed in fully diŠeren-tiated mouse adipocytes. Fsp27 and cell death-inducing DFF45-like eŠector (CIDE) C, the human homologue of fsp27, belong to the CIDE family. Fsp27, which is highly expressed in mouse white and brown adipose tissues, was recently reported to be a lipid droplet (LD)-binding protein that promotes lipid accumulation in adipocytes. In contrast, we showed that fsp27 was also expressed in the fatty liver of the ob/ob type II diabetes model mouse. The expression of fsp27 was markedly decreased in livers lacking the nuclear receptor peroxisome proliferator-activated receptor g (PPARg). A functional PPAR response element site was identiˆed in the fsp27 promoter region. Forced expression of fsp27 in hepatocytes in vitro or in vivo led to increased LD through increased triglyceride levels. The current status of the physiological roles of the PPARg-fsp27 signal in fatty liver are discussed along with its signiˆcance as a factor involved in the development of metabolic disorders.