Table 1.
Overview of the role of Sirtuins in adipose tissue remodeling.
| Adipocyte fate | Lipid mobilization | AT inflammation | AT fibrosis | AT browning | |
|---|---|---|---|---|---|
| SIRT1 | ↓ Adipogenesis (24–26) by promoting CACUL1 binding to PPARγ-responsive site to repress PPARγ (24) | ↑ Lipolysis by activating AMPK (20), and repressing PPARγ (27) and FOXO1-mediated expression of ATGL (28) | ↓ Pro-inflammatory responses (29–43) by inhibiting NF-κB signaling pathway (29, 36–42), NLRP3 (34, 35), mTOR/S6K1 pathway (43), STAT3 (39), FOXO1-C/EBPα transcriptional complex (44), and PPARγ (45) | ↓ ECM and macrophage infiltration (39) | ↑ White AT browning (20, 27, 46–49) by deacetylating PPARγ (27, 48) and activating AMPK (20) and FGF21 (49) |
| Not related to brown adipocyte differentiation (29) | |||||
| SIRT1 deficiency suppresses adipogenesis by increasing the acetylation of NCOR1 during the early stage of mESCs to adipocyte differentiation (50) | SIRT1 deficiency ↑ ECM by suppressing the expression of leptin, adiponectin, and MMP3/13, and elevating the expression of Collagen 6A3 (51) | ||||
| ↑ Beige adipocyte differentiation of elderly AT-MSC via p53/p21 pathway (52) | ↑ Anti-inflammatory responses (46, 53) by deacetylating the transcription factor NFATc1 (53) | ||||
| ↓ Lipid droplet number, lipid accumulation, and adipogenesis by preventing the proper induction of PPARγ2 and C/EBPα in visceral AT-derived stem cells (26) | SIRT1 deficiency ↑ brown AT degeneration by decreasing PGC-1α, UCP1, and CPT1b (54) | ||||
| SIRT2 | ↓ Adipogenesis (55, 56) by deacetylating FOXO1 and promoting FOXO1 binding to PPARγ (56) | ↑ Lipolysis (55, 57) by deacetylating PGC-1α (58) | Not available (N/A) | N/A | N/A |
| ↓ Lipid droplet number, lipid accumulation, and adipogenesis, by preventing the proper induction of PPARγ2 and C/EBPα in visceral AT-derived stem cells (26) | |||||
| SIRT3 | ↑ Brown adipocyte differentiation through PGC-1α (59) | ↓ Lipid droplet size and accumulation (21, 60) by activating the AMPK-ULK1 pathway (60) | ↓ Pro-inflammatory responses by inhibiting NLRP3 (61) | SIRT3 deficiency ↑ collagen VI (61) | SIRT3 deficiency ↑ brown AT whitening (21, 61, 62), suppresses UCP1 (61) and perilipin-1 (61, 62) and promotes collagen IV (61) |
| SIRT3 deficiency promotes adipogenic differentiation by decreasing FOXO3a (63) | |||||
| No effect on adipogenesis in 3T3-L1 cells (64) | |||||
| SIRT4 | ↑ Adipocyte differentiation by interacting coordinately with the transcription factors including C/EBPβ, E2F-1, and HOXA5 (65) | ↑ Lipogenesis by repressing FAO via deacetylating MCD (66) | N/A | N/A | N/A |
| ↑ Adipogenesis by promoting branched-chain amino acid catabolism by MCC1 (64) | |||||
| SIRT5 | ↓ Adipocyte differentiation (67, 68), lipid synthesis, and lipid deposition by activating AMPK and repressing MAPK (68) | SIRT5 deficiency ↓ FAO (69) and ↑ lipolysis by stimulating ATGL (67) | N/A | N/A | SIRT5 deficiency ↓ AT browning (22, 69) by decreasing the expression of thermogenic genes including UCP1, CIDEA, COX7A1, CPT1b, and MCAD (21) |
| ↑ Adipogenesis modestly in 3T3-L1 cells (64) | No effect on lipolysis (70) | ||||
| SIRT6 | ↓ Adipocyte differentiation by activating AMPKα (71) | ↑ Lipolysis via specific reduction of PPARγ signaling (72) | ↓ Pro-inflammatory responses (23, 73, 74) by increasing the occupancy of c-Jun (73) and inhibiting NF-κB signaling pathway (74) | N/A | SIRT6 deficiency ↓ AT browning (75–78) by decreasing UCP1 (23, 76) and PGC-1α (76) |
| ↑ Adipogenesis (79) by inhibiting KIFC and enhancing CK2; SIRT6 deficiency leads to a severe adipogenesis defect and reduced expression of adipogenic markers, including PPARγ, C/EBPα, aP2, and adiponectin | SIRT6 deficiency ↓ lipolysis by suppressing the expression of ATGL by regulating FOXO1 acetylation (73) | ↑ Anti-inflammatory responses (76, 80) | |||
| SIRT7 | ↑ Adipogenesis by suppressing SIRT1 (81) | N/A | N/A | N/A | N/A |
CACUL1, CDK2-associated cullin 1; PPARγ, peroxisome proliferator-activated receptor γ; FOXO, forkhead box O; ATGL, adipose triglyceride lipase; NLRP3, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3; mTOR, mammalian target of rapamycin; ECM, extracellular matrix; AT, adipose tissue; NCOR1, nuclear receptor corepressor 1; mESCs, mouse embryonic stem cells; NF-κB, nuclear factor-κB; MMP3/13, matrix metalloproteinases 3/13; PGC-1α, proliferator-activated receptor-γ coactivator-1α; UCP1, uncoupling protein 1; CPT1b, carnitine palmitoyltransferase 1b; ULK1, unc-51-like kinase 1; E2F-1, E2F transcription factor-1; HOXA5, homeobox A5; MCC1, methylcrotonyl-CoA carboxylase 1; FAO, fatty acid oxidation; CIDEA, cell death-inducing DFFA-like effector a; COX7A1, cytochrome c oxidase subunit 7A1; MCAD, medium-chain acyl-coenzyme A dehydrogenase; KIFC, kinesin family member C; CK2, casein kinase 2; AMPK, adenosine 5′-monophosphate-activated protein kinase; MCD, deacetylating malonyl CoA decarboxylase; N/A, Not available.