Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/33835
Title: Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate
Author: Vilà Brau, Anna
Sousa-Coelho, Ana Luísa de
Gonçalves, Joana F.
Haro Bautista, Diego
Marrero González, Pedro F.
Keywords: Àcids grassos
Fetge
Regulació genètica
Lípids
Fatty acids
Liver
Genetic regulation
Lipids
Issue Date: 6-Dec-2012
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: FSP27 (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, while 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 since: 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 auto-regulation between short- and long-term fasting, by which free fatty acids delivered to the liver during early fasting are accumulated/exported by FSP27/CIDEC, while over longer periods of fasting they are degraded in the mitochondria through the carnitine palmitoyl transferase (CPT) system.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1194/jlr.M028472
It is part of: Journal of Lipid Research, 2012, vol. 54, num. 3, p. 592-601
Related resource: http://dx.doi.org/10.1194/jlr.M028472
URI: http://hdl.handle.net/2445/33835
ISSN: 0022-2275
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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