Unknown,Transcriptomics,Genomics,Proteomics

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SIRT4 KO livers microarray


ABSTRACT: Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator activated receptor (PPAR ) target genes associated with fatty acid catabolism. Accordingly, primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4 KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of mitochondrial signaling in the liver and functions as an important regulator of lipid metabolism. SIRT4 knockout (KO) and wild-type (WT) littermates (male; n 6 per genotype; 7- to 8-month-old littermates) were sacrificed after a 16-h overnight fast. Samples were individually hybridized on Affymetrix Mouse Genome 430 2.0 GeneChips by the Biopolymers Facility (Harvard Medical School).

ORGANISM(S): Mus musculus

SUBMITTER: Gaelle Laurent 

PROVIDER: E-GEOD-56321 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation.

Laurent Gaëlle G   de Boer Vincent C J VC   Finley Lydia W S LW   Sweeney Meredith M   Lu Hong H   Schug Thaddeus T TT   Cen Yana Y   Jeong Seung Min SM   Li Xiaoling X   Sauve Anthony A AA   Haigis Marcia C MC  

Molecular and cellular biology 20130916 22


Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proli  ...[more]

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