Table 1.
Deacetylated targets of sirtuins relevant to the polyol-fructose-uric acid pathway
| Deacetylation Target (Refs.) | Sirtuins | How Sirtuins Acts | Result |
|---|---|---|---|
| PTP1B (33) | SIRT1 | Inactivates PTP1B (negative regulator of insulin receptor) | Increases insulin signaling and prevents leptin resistance |
| FoXO1 (34, 35, 36) | SIRT1, SIRT2,SIRT6 | Translocates FoXO1 to nucleus with transcription of target genes | Improves insulin signaling, suppresses lipogenesis, and increases lipolysis |
| FoXO3a (37) | SIRT2 | Activates antioxidant response | Suppresses oxidative stress |
| P3K/AKT pathway (38) | SIRT1 | Translocation of Akt to cell membrane and activation | Improves cell signaling and metabolism |
| Complex I and II (39) | SIRT1-SIRT3 | Activation of electron transfer chain | Improves insulin sensitivity and reduces oxidative stress |
| CRCT2 (40, 41) | SIRT1 | Ubiquitination of deacetylated CRCT2 | Suppresses lipogenesis |
| SREBP-1 (42) | SIRT1 | Inhibits transactivation | Suppresses lipogenesis |
| PPARγ (43) | SIRT1, SIRT2 | Reduced PPARγ activity | Increases lipid oxidation |
| PGC-1α (44, 45) | SIRT1, SIRT2, | Activates transcriptional activity and modulates mitochondrial biogenesis | Stimulates autophagy and reduces oxidative stress |
| Stearoyl-CoA desaturaselong chain acy-CoA dehydrogenase (46) | SIRT3 | Inactivation | Reduces lipogenesis |
| LXR (47) | SIRT1 | Upregulation | Reduces lipogenesis |
| NRF2 (48, 49) | SIRT1, SIRT2 | Transactivation of target antioxidant genes (MnSOD, catalase, heme oxygenase) | Reduces oxidative stress |
| NF-κB RelA/p65 (50, 51,52) | SIRT1, SIRT3 | Inactivation and ubiquitination of NF-κB | Anti-inflammatory effect and suppression of NLRP3 inflammasome activation |
| AP1 (53) | SIRT1 | Suppresses AP1 transcriptional activity and reduces COX2 and PGE production in macrophages | Anti-inflammatory effect |
| LKB1 (42, 41) | SIRT1 | Activates AMPK | Increases lipid oxidation |
| HIF-1α (54, 55) | SIRT1, SIRT6 | Suppresses glycolytic enzymes | Switch from aerobic glycolysis to lipid oxidation |
| AMPK (31) | Activation of AMPK and PGC1-α | Improves mitochondrial function and metabolism | |
| P53 (56) | SIRT6 | Repression of p53activity and inhibition of Fas/FaL signaling | Reduces apoptosis and reduces oxidative stress |
| STAT3 (57) | SIRT1 | Suppression of IL-6/ STAT pathway | Reduces inflammation |
| HSP90 (58) | SIRT2 | Disassociation of HSP90 with glucocorticoid receptor | Reduces inflammatory cytokines |
Sirtuin targets for deacetylation and how they improve features of metabolic syndrome and inflammation are shown. AkT, protein kinase B; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; AP1, activator protein 1; CRTC2, CREBP-regulated transcription co-activator 2; HIF1-α, hypoxia inducible factor 1-α; FoxO, forkhead transcription factor O; HSP90, heat shock protein 90; LKB1, liver kinase B1; LXR, liver X receptor; NRF2, nuclear factor E2-related factor 2; PGC1-α, peroxisome proliferator-activated receptor γ coactivator 1-α; PPARγ, peroxisome proliferator-activated receptor-γ; PTP1B, protein tyrosine phosphatase 1B; SREBP-1, sterol regulatory element binding protein 1; STAT3, activator of transcription 3.