title: Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Vilà-Brau
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: De Sousa-Coelho
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
authors.forename: Joana F
authors.initials: JF
authors.lastname: Gonçalves
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Haro
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona, Barcelona, Spain.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Marrero
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C472088:CIDEC protein, human; D005227:Fatty Acids; D011506:Proteins; C525805:fat-specific protein 27, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1