Introduction; Chapter 1: Biochemistry and Enzymology of Sirtuins; 1.1 Biochemistry and Enzymology of Sirtuins; 1.1.1 Definition of Sirtuins; 1.1.2 Sirtuin Reactivity; 1.1.3 Sirtuin Substrates; 1.1.4 Sirtuin Reactions and Mechanisms; 1.1.5 Mechanisms of SIRT1-7 Regulation; 1.1.5.1 Transcriptional Regulation of Sirtuins; 1.1.5.2 Regulation by Posttranslational Modification; 1.1.5.3 Regulation by Protein Protein Interactions; 1.1.5.4 Regulation by Alterations in NAD+ Metabolism; 1.1.5.5 Regulation by Compartmentalization; 1.1.6 Assays of Sirtuins

1.1.6.1 Fluor de Lys Fluorescence Assay1.1.6.2 SIRT1 Fluorescence Polarization Assay; 1.1.6.3 Radioisotopic Assays; 1.1.6.4 Mechanism-Based Affinity Capture of Sirtuins; References; Chapter 2: NAD+ as a Pharmacological Tool to Boost Sirtuin Activity; 2.1 Introduction; 2.2 NAD Biosynthesis; 2.2.1 Primary Biosynthesis from Tryptophan; 2.2.2 Preiss-Handler Pathway and NAD Salvage; 2.2.3 Nicotinamide Riboside; 2.3 NAD Utilization; 2.3.1 Sirtuins; 2.3.2 Poly(ADP-Ribose)Polymerases; 2.3.3 Cyclic ADP-Ribose Synthases; 2.4 Pharmacological Opportunities to Activate Sirtuins; 2.5 Conclusion; References

Chapter 3: Protein Lysine Acylation: Abundance, Dynamics and Function3.1 Introduction; 3.2 Lysine Acetylation; 3.2.1 Function of Protein Acetylation; 3.3 Lysine Formylation; 3.4 Lysine Propionylation and Butyrylation; 3.5 Lysine Malonylation, Succinylation and Glutarylation; 3.5.1 Malonylation and Succinylation; 3.5.2 Glutarylation; 3.6 Lysine Crotonylation; 3.7 Regulation of Lysine Acylation; 3.7.1 Acetyltransferases; 3.7.2 Histone Deacetylases; 3.7.3 Non-enzymatic Lysine Acylation; 3.8 Proteomic Studies: Mapping the Cellular Acylome; 3.8.1 Acetylation; 3.8.2 Succinylation

3.8.3 Glutarylation3.9 Conclusion; References; Chapter 4: SIRT1 in Metabolic Health and Disease; 4.1 Introduction; 4.2 SIRT1 Biology; 4.2.1 Basic Structure and Localization; 4.2.2 SIRT1 Regulation; 4.2.2.1 Regulation at the Expression Level; 4.2.2.2 Regulation by NAD+ and NAM; 4.2.2.3 Regulation by Post-translational Modifications; 4.2.2.4 Regulation by Protein Interactions; 4.2.3 SIRT1 Functions; 4.3 What Animal Models Have Taught Us; 4.3.1 SIRT1 and Whole Body Metabolism; 4.3.2 SIRT1 Functions in the Liver; 4.3.2.1 SIRT1 and Hepatic Glucose Production

4.3.2.2 SIRT1 and Hepatic Lipid Metabolism4.3.2.3 SIRT1 and Cholesterol Metabolism; 4.3.3 SIRT1 Functions in Skeletal Muscle; 4.3.4 SIRT1 Functions in Adipose Tissues; 4.3.4.1 White Adipose Tissue; 4.3.4.2 Brow Adipose Tissue; 4.3.5 SIRT1 Functions in the Pancreas; 4.3.6 SIRT1 and Food Intake Behaviour; 4.4 Conclusions and Future Perspectives; References; Chapter 5: Deacetylation by SIRT3 Relieves Inhibition of Mitochondrial Protein Function; 5.1 Introduction; 5.2 Acetylation Abrogates Lysine Charge; 5.3 Strategy; 5.4 Structural Regulation; 5.4.1 MDH2; 5.4.2 HMGCS2