title: Histone Deacetylase SIRT1 Controls Proliferation, Circadian Rhythm, and Lipid Metabolism during Liver Regeneration in Mice.
abstract: Liver regeneration offers a distinctive opportunity to study cell proliferation in vivo Mammalian silent information regulator 1 (SIRT1), a NAD+-dependent histone deacetylase, is an important regulator of various cellular processes, including proliferation, metabolism, and circadian rhythms. In the liver, SIRT1 coordinates the circadian oscillation of clock-controlled genes, including genes that encode enzymes involved in metabolic pathways. We performed partial hepatectomy in WT and liver-specific Sirt1-deficient mice and analyzed the expression of cell cycle regulators in liver samples taken at different times during the regenerative process, by real time PCR, Western blotting analysis, and immunohistochemistry. Lipidomic analysis was performed in the same samples by MS/HPLC. We showed that G1/S progression was significantly affected by absence of SIRT1 in the liver, as well as circadian gene expression. This was associated to lipid accumulation due to defective fatty acid beta-oxidation. Our study revealed for the first time the importance of SIRT1 in the regulation of hepatocellular proliferation, circadian rhythms, and lipid metabolism during liver regeneration in mice. These results represent an additional step toward the characterization of SIRT1 function in the liver.
authors.affiliation: From the Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy, marina_bellet@yahoo.com.
authors.forename: Marina Maria
authors.initials: MM
authors.lastname: Bellet
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, California 92697.
authors.forename: Selma
authors.initials: S
authors.lastname: Masri
authors.affiliation: Health Sciences, Waters Corporation, Milford, Massachusetts 01757, and.|Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington DC 20057.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.affiliation: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, Irvine, California 92697.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
authors.affiliation: From the Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.
authors.forename: Maria Agnese
authors.initials: MA
authors.lastname: Della Fazia
authors.affiliation: From the Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy, giuseppe.servillo@unipg.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Servillo
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D008107:Liver Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008115:Liver Regeneration; D051379:Mice; D018345:Mice, Knockout; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D056564:Sirtuin 1
keywords: G1/S cyclin; circadian rhythm; clock gene; lipid metabolism; partial hepatectomy; proliferation; sirtuin