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

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 α (PPARα) 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.

journal_name

Mol Cell Biol

authors

Laurent G,de Boer VC,Finley LW,Sweeney M,Lu H,Schug TT,Cen Y,Jeong SM,Li X,Sauve AA,Haigis MC

doi

10.1128/MCB.00087-13

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

4552-61

issue

22

eissn

0270-7306

issn

1098-5549

pii

MCB.00087-13

journal_volume

33

pub_type

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