Table 1.
Pathophysiological roles of USPs in metabolic disorders.
| Disease | USPs | Expressing Cells/Tissues | Restorative/Deteriorative | Direct Targets | References |
|---|---|---|---|---|---|
| Obesity | USP2 | Adipocyte | Deteriorative | Cyclin D | [46] |
| USP7 | Adipocyte | Deteriorative | SREBP1c | [45] | |
| USP15 | Adipocyte | Deteriorative | Keap1 | [42] | |
| USP19 | Adipocyte | Deteriorative | ? | [49] | |
| USP20 | Hepatocyte | Deteriorative | HMGCR | [50] | |
| USP53 | Adipose tissue | Restorative | ? | [53] | |
| T1DM | USP18 | β-cell | Restorative | ? | [58] |
| USP22 | Treg | Restorative | FoxP3 | [56] | |
| T2DM | USP1 | β-cell | Deteriorative | ? | [69] |
| USP22 | β-cell | Restorative | Sirt-1 | [68] | |
| USP2 | Adipose tissue macrophage | Restorative | ? | [78,79] | |
| USP19 | Adipocyte | Deteriorative | ? | [49] | |
| USP9X | Myocyte | Restorative | AMPKα2 | [87] | |
| USP20 | Myocyte | Restorative | β2 adrenoreceptor | [94] | |
| USP21 | Myocyte | Deteriorative | DNA-PKcs, ACLY | [84] | |
| USP33 | Myocyte | Restorative | β2 adrenoreceptor | [94,95] | |
| USP2 | Hepatocyte | Deteriorative | C/EBPα | [102] | |
| USP4 | Hepatocyte | Restorative | TAK1 | [109] | |
| USP7 | Hepatocyte | Restorative | IRS1 | [99] | |
| Restorative | PPARγ | [100] | |||
| Restorative | FoxO1 | [101] | |||
| USP10 | Hepatocyte | Restorative | Sirt-6 | [114] | |
| USP14 | Hepatocyte | Deteriorative | CBP | [103] | |
| Deteriorative | FASN | [108] | |||
| USP18 | Hepatocyte | Restorative | TAK1 | [111] | |
| USP20 | Hepatocyte | Deteriorative | HMGCR | [50] | |
| USP2 | Hypothalamus | Restorative | ? | [117] | |
| Diabetic nephropathy | USP2 | Kidney | ? | ? | [130] |
| USP7 | Kidney | ? | H2A, H2B? | [132] | |
| USP9X | Renal epithelial cell | Restorative | Connexin43 | [139] | |
| Mesangial cell | Restorative | Nrf2 | [141] | ||
| USP14 | Podocyte | Deteriorative | SPAG5-AS | [147] | |
| USP15 | Podocyte | Deteriorative | Keap1 | [150] | |
| USP16 | Kidney | ? | H2A, H2B? | [132] | |
| USP21 | Kidney | ? | H2A, H2B? | [132] | |
| USP22 | Kidney | ? | H2A? H2B | [132] | |
| Mesangial cell | Restorative | Sirt-1 | [135] | ||
| Renal epithelial cell | Restorative | Sirt-1 | [136] | ||
| Kidney | Deteriorative | ? | [137] | ||
| Podocyte | Deteriorative | ? | [138] | ||
| USP36 | Renal epithelial cell | Deteriorative | DOCK4 | [144] | |
| Diabetic retinopathy | USP1 | Vascular endothelial cells | Deteriorative | ? | [160] |
| USP14 | Müller cells | Deteriorative | TGF-β receptor, IκBα, Nrf2 | [162] | |
| USP48 | Pigment epithelial cell | Restorative | NFκBp65 | [159] | |
| Diabetic neuropathy | USP5 | Spinal dorsal horn | Deteriorative | Cav3.2 | [167] |
| Diabetic myopathy | USP19 | Myocyte | ? | ? | [174] |
| USP21 | Myocyte | Deteriorative | DNA-PKcs, ACLY | [84] | |
| Diabetic cardiomyopathy | USP10 | Cardiomyocyte | Restorative | NICD1 | [176] |
| Diabetic foot ulcers | USP7 | Vascular endothelial cells | Deteriorative | p53 | [179] |
| NAFLD | USP2 | Hepatocytes | Deteriorative | FASN | [198,199] |
| USP4 | Hepatocytes | Restorative | TAK1 | [109] | |
| USP7 | Hepatocyte | Restorative | IRS1 | [99] | |
| Deteriorative | Mdm2 | [185] | |||
| Deteriorative | PPARγ | [100] | |||
| Deteriorative | ZNF638, | [184] | |||
| CREB, | |||||
| SREBP1c | |||||
| USP10 | Hepatocyte | Restorative | Sirt-6 | [114] | |
| Restorative | ? | [191] | |||
| USP11 | Hepatocyte | Deteriorative | KLF4 | [201] | |
| USP14 | Hepatocyte | Deteriorative | FASN | [108] | |
| USP18 | Hepatocyte | Restorative | TAK1 | [111] | |
| USP19 | Hepatocyte | Deteriorative | SOAT1 | [204] | |
| USP20 | Hepatocyte | Deteriorative | HMGCR | [50] | |
| USP22 | Hepatocyte | Restorative | Sirt-1 | [195] | |
| Hepatocyte | Deteriorative | PPARγ | [193] | ||
| Atherosclerosis | USP2 | Hepatocyte | Restorative | IDOL | [212] |
| USP9X | Macrophage | Restorative | SR-A1 | [223] | |
| USP14 | Vascular endothelial cell | Restorative | NLRC5 | [221] | |
| Vascular smooth muscle cell | Deteriorative | PMSD7 | [217] | ||
| USP17 | Vascular smooth muscle cell | Deteriorative | ? | [224] | |
| USP20 | Vascular smooth muscle cell | Restorative | TRAF6 | [215] | |
| Restorative | RIPK1 | [216] | |||
| Liver | Deteriorative? | HMGCR | [50] | ||
| Cushing disease | USP8 | Corticotroph adenoma | Deteriorative | ? | [228,229,230,231,232,233,234,235,236,237,238] |
| USP48 | Corticotroph adenoma | Deteriorative | ? | [237] |
Metabolic disorders, USP species, USP-expressing cells or tissues, pathological roles of USPs, direct molecular targets, and references are shown.