Table 1.
Summary of adipose mTOR signaling on thermogenetic effects in rodents
| Refs | mTOR related molecules | Mouse model/ exp. condition | Activity of mTOR signaling | Tissue affected | Phenotypes |
|---|---|---|---|---|---|
| Liu et al.2016 [79] |
Rapamycin-treated mice (7days) under cold exposure Rapamycin-treated mice (2 days) under cold exposure |
mTORC1 inhibited |
WAT BAT |
Thermogenic gene expression ↓ Thermogenic gene expression ↓ Core body temperature ↓ |
|
| Tran et al.2016 [80] | Rapamycin-treated mice (2 weeks) under CL Stimulation (24 hours) | mTORC1 inhibited | WAT |
Cold tolerance ↓ Thermogenic gene expression ↓ Beige fat gene expression ↓ |
|
| Makki et al.2014 [81] | Diet-induced obese mice with chronic treatment of rapamycin (22 weeks) | mTORC1 inhibited | BAT |
Energy expenditure ↑ Oxygen consumption ↑ BAT activity ↑ |
|
| Labbe et al.2016 [71] | Raptor | raptor-/- mice (Adipoq-Cre) under cold exposure (2 weeks) | mTORC1 inhibited | BAT |
Systemic oxygen consumption ↓ BAT mass ↓ Nucleotide synthesis ↓ Mitochondrial biogenesis ↓ TCA cycle activity ↓ Thermogenic gene ↓ |
| Lee et al. 201 6[72] | Raptor | raptor-/- mice (Adipoq-Cre) with HFD | mTORC1 inhibited |
WAT BAT |
Expression of Ucp1 in WAT ↑ Expansion of WAT and BAT ↓ No changes on energy expenditure |
| Liu et al.2016 [79] | Raptor | raptor-/- mice (Adiponq-Cre) under cold exposure (7 days) | mTORC1 inhibited |
WAT BAT |
Expression of Ucp1 ↓ Mitochondrial related genes ↓ |
| Tran et al.2016 [80] | Raptor | raptor-/- mice (Adiponq-Cre) with CL stimulation (24h hours) | mTORC1 inhibited | WAT |
Thermogenic gene ↓ Lipolysis ↓ Adipocyte size ↑ |
| Polak et al.2008 [86] | Raptor | raptor-/- mice (aP2-Cre) at thermoneutrality | mTORC1 inhibited | WAT |
Oxygen consumption ↑ Ucp1 expression ↑ |
| Zhang et al.2018 [87] | Raptor | raptor-/- mice (Adiponectin-Cre) under cold exposure (2 days) | mTORC1 inhibited |
WAT BAT |
Beige adipogenesis ↑ Thermogenic gene ↑ Thermogenic gene ↓ |
| Shan et al.2016 [73] | mTOR | mTOR-/- mice (Adipoq-Cre) with ND | mTORC1 inhibited |
WAT BAT |
Mass of BAT and WAT ↓ Thermogenic genes in WAT ↑ No changes on energy expenditure |
| Um et al.2004 [96] | S6K | S6K1-/- mice (whole body) under ND or HFD | mTORC1 inhibited | Whole body |
Lipolysis in WAT ↑ Mitochondria numbers in WAT ↑ Oxidative phosphorylation in WAT ↑ Metabolic related genes in WAT ↑ |
| Le Bacquer et al. 2007 [97] | 4EBPs | 4E-BP1/ 2-/- mice (whole body) under ND or HFD | mTORC1hyper-activated | Whole body |
Oxygen consumption ↓ Lipolysis in WAT ↓ |
| Liu et al.2014 [57] | Grb10 | Grb10-/-mice (Adipoq-Cre) under cold exposure | mTORC1hyper-activated | BAT |
Core body temperature ↓ Cold-induced thermogenic genes ↓ |
| Meng et al.2017 [98] [99] | Rheb | Rheb-/-mice (Adipoq-Cre) under ND or HFD, with or without cold exposure | mTORC1 inhibited |
WAT BAT |
Lipolysis ↑ Beige adipocytes in WAT ↑ Energy expenditure ↑ Thermogenic gene expression in BAT ↓ |
| Magdalon et al.2016 [100] | TSC1 | TSC1-/- mice (Adipoq-Cre) under ND | mTORC1hyper-activated | WAT |
Lipolysis ↑ Ucp1 expression ↑ Mitochondrial oxidative activity ↑ Fatty acid oxidation ↑ PGC-1α and PPARα |
| Xiang et al.2015 [101] | TSC1 | TSC1-/- mice (aP2-Cre) under ND | mTORC1hyper-activated | BAT |
Brown adipocyte genes ↓ White adipocyte genes ↑ |
| Albert et al.2016 [103] | Rictor | rictor-/- mice (aP2-Cre) under cold exposure |
mTORC2 inhibited |
BAT |
Cold tolerance ↓ Glucose uptake ↓ Glycolysis ↓ |
| Kumar et al.2010 [104] | Rictor |
rictor-/- mice (Ap2-Cre) |
mTORC2 inhibited |
BAT WAT |
Glucose uptake ↓ Glycolysis ↓ |
| Hung et al.2014 [107] | Rictor | rictor-/- mice (Myf5-Cre) under cold exposure | mTORC2 inhibited | BAT |
Mitochondrial activity ↑ Ucp1 expression ↑ |
| Tang et al.2016 [108] | Rictor | rictor -/- mice (Adipoq-Cre) | mTORC2 inhibited | WAT |
Lipogenesis ↓ Glucose uptake ↓ |
| Sanchez et al.2018 [109] | Akt2 | Akt2-/- mice (Ucp1-Cre) under cold exposure | mTORC2 inhibited | BAT |
Lipid synthesis and oxidation ↓ Ucp1 expression ↓ |
| Sanchez et al.2019 [110] |
Akt1 Akt2 |
Akt1and Akt2-/- mice (Ucp1-Cre/Ucp1-CreER/Myf5-Cre) | mTORC2 inhibited | BAT |
Lipid droplets in BAT ↓ Ucp1 expression ↓ |
Abbreviations: BAT Brown adipose tissue, CL CL-316243, Grb10 Growth factor receptor-bound protein 10, HFD High fat diet, ND Normal diet, Raptor Regulatory associated protein of mTOR, Rheb Ras homolog enriched in brain, Rictor Raptor-independent companion of mTOR, S6K Ribosomal S6 kinase, TSC1 Tuberous sclerosis complex 1, WAT White adipose tissue, 4E-BPs Eif4e-binding proteins
Note: ↑ increased; ↓ decreased