FSP27 [cell death-inducing DFFA-like effector c (CIDEC) in humans] is a protein 
associated with lipid droplets that downregulates the fatty acid oxidation (FAO) 
rate when it is overexpressed. However, little is known about its physiological 
role in liver. Here, we show that fasting regulates liver expression of Fsp27 in 
a time-dependent manner. Thus, during the initial stages of fasting, a maximal 
induction of 800-fold was achieved, whereas during the later phase of fasting, 
Fsp27 expression decreased. The early response to fasting can be explained by a 
canonical PKA-CREB-CRTC2 signaling pathway because: i) CIDEC expression was 
induced by forskolin, ii) Fsp27 promoter activity was increased by CREB, and 
iii) Fsp27 expression was upregulated in the liver of Sirt1 knockout animals. 
Interestingly, pharmacological (etomoxir) or genetic (Hmgcs2 interference) 
inhibition of the FAO rate increases the in vivo expression of Fsp27 during 
fasting. Similarly, CIDEC expression was upregulated in HepG2 cells by either 
etomoxir or HMGCS2 interference. Our data indicate that there is a kinetic 
mechanism of autoregulation between short- and long-term fasting, by which free 
FAs delivered to the liver during early fasting are accumulated/exported by 
FSP27/CIDEC, whereas over longer periods of fasting, they are degraded in the 
mitochondria through the carnitine palmitoyl transferase system.