Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating 
hyperglycemia and type 2 diabetes. However, the mechanism of action of these 
agonists is still under investigation. The lipid droplet-associated proteins 
FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated 
with hepatic steatosis and insulin sensitivity. Here, we evaluated the 
expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins 
by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice 
with diet-induced obesity were treated with the PPARγ or PPARα agonist, 
pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic 
mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in 
mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate 
treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein 
expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the 
context of insulin resistance or treatment with PPAR agonists. However, LSDP5 
was highly expressed in humans, with elevated expression observed in the fatty 
liver. We concluded that fenofibrate greatly decreased hepatic TG content and 
FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential 
regulatory role for fenofibrate in the amelioration of hepatic steatosis.