NAD+-dependent Sirtuin 1 and 6 Proteins Coordinate a Switch from Glucose to Fatty Acid Oxidation during the Acute Inflammatory Response

Liu, Tie Fu; Vachharajani, Vidula; Yoza, Barbara K.; McCall, Charles E.

doi:10.1074/jbc.m112.362343

Cited by 298 publications

(332 citation statements)

References 38 publications

Supporting

Mentioning

317

Contrasting

Unclassified

Order By: Relevance

“…Regarding the modulator of PGC-1␣ deacetylation, we propose that SIRT1 and SIRT6 may coordinate each other. In line with this, it has been shown that SIRT1 and SIRT6 coordinate the switch from glucose to fatty acid ␤-oxidation in response to an acute inflammation (27). In addition, we observed that SIRT1 protein levels first increased at 7 days and then declined at 21 days (biphasic change).…”

Section: H354supporting

confidence: 89%

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Fukushima

Alrob

Zhang

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Fukushima A, Alrob OA, Zhang L, Wagg CS, Altamimi T, Rawat S, Rebeyka IM, Kantor PF, Lopaschuk GD. Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart. Am J Physiol Heart Circ Physiol 311: H347-H363, 2016. First published June 3, 2016; doi:10.1152/ajpheart.00900.2015.-Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid ␤-oxidation rates increased in 21-day vs. 1-and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and ␤-hydroxyacylCoA dehydrogenase (␤-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid ␤-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and ␤-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-␥ coactivator-1␣, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxiainducible factor-1␣, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation.Listen to this article's corresponding podcast at http://ajpheart.podbean. com/e/acetylation-control-of-energy-metabolism-in-newborn-hearts/. myocardial fatty acid oxidation; lysine acetylation; lysine succinylation; newborn heart NEW & NOTEWORTHYThe present study is the first showing that alterations in acetylation and succinylation control of metabolic enzymes contribute to the dramatic shift in cardiac energy metabolism from glycolysis to fatty acid ␤-oxidation seen during maturation. Our results suggest that lysine acetylation enhances cardiac fatty acid ␤-oxidation and inhibits glycolysis during maturation.OVER 1% OF NEWBORNS ARE DIAGNOSED with congenital heart disease (CHD), with one-third of these needing surgery within the first months of life (36). Despite the major advance...

show abstract

Section: H354supporting

confidence: 89%

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Fukushima

Alrob

Zhang

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Although we did not find differences in sirtuin 1 expression in the skeletal muscle that correlate with the gene expression increase detected in fP8WR mice, we did find a significant increase in PGC-1α and in the sirtuin 1 activator AMPK in these mice. Interestingly, the activation of the sirtuin 1-AMPK-PGC-1α pathway is involved in mitochondrial biogenesis (Chen et al 2008;Liu et al 2012) and has been previously proposed as a possible target of molecular changes induced by exercise (Liu and Fielding 2011;Canto and Auwerx 2009). Indeed, evidence suggests that moderate levels of regular physical activity increase a larger number of mitochondrial biogenesis-related gene expression in aged subjects, though to a lesser extent than in younger individuals (Bori et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Long-term wheel running changes on sensorimotor activity and skeletal muscle in male and female mice of accelerated senescence

Sanchez‐Roige

Lalanza

Álvarez-López

et al. 2014

AGE

View full text Add to dashboard Cite

The senescence-accelerated mouse prone 8 (SAMP8) is considered a useful non-transgenic model for studying aspects of aging. Using SAM resistant 1 (SAMR1) as controls, the long-term effects of wheel running on skeletal muscle adaptations and behavioral traits were evaluated in senescent (P8) and resistant (R1) male and female mice. Longterm wheel running (WR) led to increases in locomotor activity, benefits in sensorimotor function, and changes in body weight in a gender-dependent manner. WR increased body weight and baseline levels of locomotor activity in female mice and improved balance and strength in male mice, compared to sedentary-control mice. WR resulted in key metabolic adaptations in skeletal muscle, associated with an increased activity of the sirtuin 1-AMP-activated protein kinase (AMPK)-PGC-1 alpha axis and changes in vascular endothelial growth factor A (Vegfa), glucose transporter type 4 (Glut4), and Cluster of Differentiation 36 (Cd36) gene expression. Overall, our data indicate that activity, balance, and strength decrease with age and that long-term WR may significantly improve the motor function in a mouse model of senescence in a gender-dependent manner.

show abstract

“…also controls inflammatory response by regulating SIRT1 activity. Anti-inflammatory action of SIRT1 is exerted by promoting a switch from glycolysis to fatty acid oxidation and by deacetylating and inactivating the p65 subunit of NF-κB, thus limiting the expression of NF-κB-dependent proinflammatory genes (Yeung et al, 2004;Liu et al, 2012). Altogether, these observations strongly indicate that the metabolic state of immune cells is critical to their function: proinflammatory cells such as M1 macrophages, activated dendritic cells, and T H 17 cells are more glycolytic, whereas anti-inflammatory cells such as T reg cells and M2 macrophages have more oxidative phosphorylation (McGettrick and O'Neill, 2013).…”

Section: Citrate In Inflammationmentioning

confidence: 99%

Citrate – new functions for an old metabolite

Iacobazzi

Infantino

2014

Biological Chemistry

226

187

View full text Add to dashboard Cite

Abstract:Citrate is an important substrate in cellular energy metabolism. It is produced in the mitochondria and used in the Krebs cycle or released into cytoplasm through a specific mitochondrial carrier, CIC. In the cytosol, citrate and its derivatives, acetyl-CoA and oxaloacetate, are used in normal and pathological processes. Beyond the classical role as metabolic regulator, recent studies have highlighted that citrate is involved in inflammation, cancer, insulin secretion, histone acetylation, neurological disorders, and non-alcoholic fatty liver disease. Monitoring changes in the citrate levels could therefore potentially be used as diagnostic tool. This review highlights these new aspects of citrate functions.

show abstract

NAD+-dependent Sirtuin 1 and 6 Proteins Coordinate a Switch from Glucose to Fatty Acid Oxidation during the Acute Inflammatory Response

Cited by 298 publications

References 38 publications

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Long-term wheel running changes on sensorimotor activity and skeletal muscle in male and female mice of accelerated senescence

Citrate – new functions for an old metabolite

Contact Info

Product

Resources

About