The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration
Open accessAbstract
raptor is a specific and essential component of mammalian TOR complex 1 (mTORC1), a key regulator of cell growth and metabolism. To investigate a role of adipose mTORC1 in regulation of adipose and whole-body metabolism, we generated mice with an adipose-specific knockout of raptor (raptor(ad-/-)). Compared to control littermates, raptor(ad-/-) mice had substantially less adipose tissue, were protected against diet-induced obesity and hypercholesterolemia, and exhibited improved insulin sensitivity. Leanness was in spite of reduced physical activity and unaffected caloric intake, lipolysis, and absorption of lipids from the food. White adipose tissue of raptor(ad-/-) mice displayed enhanced expression of genes encoding mitochondrial uncoupling proteins characteristic of brown fat. Leanness of the raptor(ad-/-) mice was attributed to elevated energy expenditure due to mitochondrial uncoupling. These results suggest that adipose mTORC1 is a regulator of adipose metabolism and, thereby, controls whole-body energy homeostasis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Knocking out the Raptor complex in adipose tissue enhances mitochondrial respiration244, but muscle-specific knockout causes muscular dystrophy in mice36.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [244]
In the citing paper
“Adipose-specific Raptor knockout mice (Raptorad−/−) have a lean phenotype and are protected against diet-induced obesity, due to enhanced energy expenditure facilitated by UCP1-mediated mitochondrial uncoupling244.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [244]
Citations
Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Self-citationAdipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor
Tontonoz, P., Hu, E., & Spiegelman, B. M. (1994) · Cell · doi:10.1016/0092-8674(94)90006-x · Cited by 3,564
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
Cited by
Sorted by citations
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
“In vitro, the inhibition of mTORC1 blocks adipogenesis and impairs the maintenance of fat cells (Gagnon et al., 2001; Kim and Chen, 2004; Polak et al., 2008), whereas overactivation of mTORC1 promotes adipogenesis (Zhang et al., 2009).”
BackgroundmTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
“However, the role of mTORC1 in adipose is complicated by the fact that Ad-RapKO mice are also resistant to diet-induced obesity due to reduced adipogenesis, suggesting mTORC1 inhibition in this tissue can have both positive and negative effects (Polak et al., 2008).”
BackgroundmTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
“Adipocyte-specific deletion of RAPTOR in mice leads to reduced WAT tissue and enhanced fatty-acid oxidatio”
BackgroundmTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737
Activation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020
“Together with recent genetic approaches to understand the role of mTORC1 in integrated physiology (Bentzinger et al., 2008; Polak et al., 2008), we are gaining important insights into the contributions of mTORC1 to the metabolic reprogramming of cells in response to the physiological or…”
mTOR is a key modulator of ageing and age-related disease
Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676
Rapamycin passes the torch: a new generation of mTOR inhibitors
Benjamin, D., Colombi, M., Moroni, C., & Hall, M. N. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3531 · Cited by 1,013
Self-citationMitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990
Morita, M., Gravel, S.-P., Chénard, V., Sikström, K., Zheng, L., Alain, T., Gandin, V., Avizonis, D., Arguello, M., Zakaria, C., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.001 · Cited by 842
“Consistent with a recent finding that a tissuespecific raptor knockout mouse exhibits decreased locomotor activity (Bentzinger et al., 2008; Polak et al., 2008), Ink1341 suppressed locomotor activity in WT mice, whereas this (D) Total mitochondrial respiration, ATP turnover, proton leak, and…”
BackgroundInfluentialRegulation of glucose transport by insulin: traffic control of GLUT4
Leto, D., & Saltiel, A. R. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3351 · Cited by 848
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803
Autophagy regulates adipose mass and differentiation in mice
Singh, R., Xiang, Y., Wang, Y., Baikati, K., Cuervo, A. M., Luu, Y. K., Tang, Y., Pessin, J. E., Schwartz, G. J., & Czaja, M. J. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39228 · Cited by 767
Protection from obesity and diabetes by blockade of TGF-β/smad3 signaling
Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., Zerfas, P., Zhigang, D., Wright, E. C., Stuelten, C., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.04.013 · Cited by 709
“Increased mitochondrial uncoupling can result in a beneficial metabolic phenotype, and mouse models demonstrating increased UCP1 expression inWAT are resistant to diet-induced obesity (Narvaez et al., 2009; Polak et al., 2008).”
BackgroundRegulation of mTORC1 and its impact on gene expression at a glance
Laplante, M., & Sabatini, D. M. (2013) · Journal of Cell Science · doi:10.1242/jcs.125773 · Cited by 697
“mTORC1 inhibition severely impairs adipogenesis and adipose cell maintenance in vitro (Cho et al., 2004; Gagnon et al., 2001; Kim and Chen, 2004; Polak et al., 2008; Yu et al., 2008; Zhang et al., 2009).”
BackgroundMitochondrial Complex III ROS Regulate Adipocyte Differentiation
Tormos, K. V., Ansó, E., Hamanaka, R. B., Eisenbart, J. D., Joseph, J., Kalyanaraman, B., & Chandel, N. S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.007 · Cited by 676
“Depletion of Raptor by RNAi results in diminished mTORC1 activity and reduced adipogenesis (Polak et al., 2008).”
Bentzinger, C. F., Romanino, K., Cloëtta, D., Lin, S., Mascarenhas, J. B., Oliveri, F., Xia, J., Casanova, E., Costa, C. F., Brink, M., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.10.002 · Cited by 640
Self-citationAn Emerging Role of mTOR in Lipid Biosynthesis
Laplante, M., & Sabatini, D. M. (2009) · Current Biology · doi:10.1016/j.cub.2009.09.058 · Cited by 642
“[28] observed that mTORC1 inactivation reduces fat accumulation in adipose tissue by promoting energy expenditure through an induction of uncoupled respiration.”
InfluentialLee, Y. S., Kim, J.-W., Osborne, O., Oh, D. Y., Sasik, R., Schenk, S., Chen, A., Chung, H., Murphy, A., Watkins, S. M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.012 · Cited by 598
D'Antona, G., Ragni, M., Cardile, A., Tedesco, L., Dossena, M., Bruttini, F., Caliaro, F., Corsetti, G., Bottinelli, R., Carruba, M. O., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.08.016 · Cited by 568
“In contrast, the absence of raptor in adipose tissue results in lean mice with enhanced mitochondrial respiration (Polak et al., 2008).”
BackgroundHepatic mTORC2 Activates Glycolysis and Lipogenesis through Akt, Glucokinase, and SREBP1c
Hagiwara, A., Cornu, M., Cybulski, N., Polak, P., Betz, C., Trapani, F., Terracciano, L., Heim, M. H., Rüegg, M. A., & Hall, M. N. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.015 · Cited by 585
Self-citationmTOR coordinates protein synthesis, mitochondrial activity and proliferation
Morita, M., Gravel, S.-P., Hulea, L., Larsson, O., Pollak, M., St-Pierre, J., & Topisirovic, I. (2015) · Cell Cycle · doi:10.4161/15384101.2014.991572 · Cited by 552
“In vivo, depletion of raptor in adipose tissue of mice induces a lean phenotype, paralleled by increased energy expenditure and increased levels of mitochondrial uncoupling proteins.(86) In addition, mTORC1 stimulates nucleotide synthesis via induction of the pentose phosphate pathway and S6K-mediated activation of ca…”
BackgroundRole of mTOR in podocyte function and diabetic nephropathy in humans and mice
Gödel, M., Hartleben, B., Herbach, N., Liu, S., Zschiedrich, S., Lu, S., Debreczeni-Mór, A., Lindenmeyer, M. T., Rastaldi, M.-P., Hartleben, G., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44774 · Cited by 547
Self-citationThe mechanistic target of rapamycin: the grand conducTOR of metabolism and aging
Kennedy, B. K., & Lamming, D. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.009 · Cited by 544
PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis
Schultze, S. M., Hemmings, B. A., Nießen, M., & Tschopp, O. (2012) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002109 · Cited by 553
“Metabolism 8, 411-424 60 Polak, P. et al. (2008) Adipose-specific knockout of”
mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice
Inoki, K., Mori, H., Wang, J., Suzuki, T., Hong, S., Yoshida, S., Blattner, S. M., Ikenoue, T., Rüegg, M. A., Hall, M. N., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44771 · Cited by 538
Self-citationMitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)
Ristow, M., & Schmeisser, K. (2014) · Dose-Response · doi:10.2203/dose-response.13-035.ristow · Cited by 534
“Adipocyte-specific disruption of RAPTOR is linked to higher rates of mitochondrial uncoupling followed by enhanced energy expenditure, which protects the mice from gaining weight (Polak et al. 2008).”
BackgroundMammalian Target of Rapamycin (mTOR): Conducting the Cellular Signaling Symphony
Foster, K. G., & Fingar, D. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.094003 · Cited by 545
The diverse functionality of NQO1 and its roles in redox control
Ross, D., & Siegel, D. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101950 · Cited by 499
Dazert, E., & Hall, M. N. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.09.003 · Cited by 460
Houde, V. P., Brûlé, S., Festuccia, W. T., Blanchard, P.-G., Bellmann, K., Deshaies, Y., & Marette, A. (2010) · Diabetes · doi:10.2337/db09-1324 · Cited by 456
“This is consistent with the recent finding that disruption of adipose mTORC1 signaling through raptor knockout increased energy expenditure (16).”
BackgroundResultmTOR in aging, metabolism, and cancer
Cornu, M., Albert, V., & Hall, M. N. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.12.005 · Cited by 455
Self-citationmTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 447
Tanti, J.-F., & Jager, J. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.07.004 · Cited by 430
Signaling pathways in obesity: mechanisms and therapeutic interventions
Wen, X., Zhang, B., Wu, B., Xiao, H., Li, Z., Li, R., Xu, X., & Li, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01149-x · Cited by 490
Insulin Stimulates Adipogenesis through the Akt-TSC2-mTORC1 Pathway
Zhang, H., Huang, J., Düvel, K., Boback, B. B., Wu, S., Squillace, R. M., Wu, C., & Manning, B. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006189 · Cited by 406
“, suggesting that some of the previous findings regarding the effects of rapamycin treatment on adipocyte differentiation could be through loss of mTORC2-mediated Akt activation, rather than inhibition of mTORC1. However, a recent study using siRNAs to the mTORC1-specific component Raptor have supported a role for mTO…”
Primary cilia regulate mTORC1 activity and cell size through Lkb1
Boehlke, C. S., Kotsis, F., Patel, V., Braeg, S., Voelker, H., Bredt, S., Beyer, T., Janusch, H., Hamann, C., Gödel, M., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2117 · Cited by 412
“In a complementary approach, co-expression of dominant-negative Raptor, a scaffold protein of mTORC”
BackgroundMolecular mechanisms of metabolic regulation by insulin in Drosophila
Teleman, A. A. (2009) · Biochemical Journal · doi:10.1042/bj20091181 · Cited by 397
Pharmacological approaches to restore mitochondrial function
Andreux, P. A., Houtkooper, R. H., & Auwerx, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4023 · Cited by 383
Self-citationm6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7
Wang, X., Wu, R., Liu, Y., Zhao, Y., Bi, Z., Yao, Y., Liu, Q., Shi, H., Wang, F., & Wang, Y. (2019) · Autophagy · doi:10.1080/15548627.2019.1659617 · Cited by 385
“Moreover, previous study shows that adipocyte-specific knockout of the MTOR component RPTOR/raptor in mice display smaller adipose tissue and increased metabolic activity compared to control littermates [34], which is similar to the phenotype in adipocyte-specific atg5 and atg7 knockout mice [5,8,9].”
ResultA Central Role for mTOR in Lipid Homeostasis
Lamming, D. W., & Sabatini, D. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.002 · Cited by 370
“Mice with an adipose-specific deletion of Raptor, which is required for mTORC1 activity, phenocopy the S6K1 knockout mice (Polak et al., 2008).”
Stanfel, M. N., Shamieh, L. S., Kaeberlein, M. R., & Kennedy, B. K. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.06.007 · Cited by 347
“An adiposespecific knockout of Raptor results in lean mice that are resistant to diet-induced obesity and insulin resistance [126].”
BackgroundmTOR couples cellular nutrient sensing to organismal metabolic homeostasis
Howell, J. J., & Manning, B. D. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.12.003 · Cited by 334
“The reduced adiposity in these mice results from both fewer and smaller adipocytes with increased energy consumption through upregulation of the mitochondrial uncoupling protein UCP1 [74], which is also seen in the adipose tissue of S6k1−/− mice [37].”
BackgroundThe metabolic regulation of aging
Finkel, T. (2015) · Nature Medicine · doi:10.1038/nm.3998 · Cited by 325
Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling
Appenzeller‐Herzog, C., & Hall, M. N. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.02.006 · Cited by 324
Self-citationThe Roles of mTOR Complexes in Lipid Metabolism
Caron, A., Richard, D., & Laplante, M. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071714-034355 · Cited by 323
McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Montalto, G., Cervello, M., Nicoletti, F., Fagone, P., Malaponte, G., Mazzarino, M. C., et al. (2012) · Oncotarget · doi:10.18632/oncotarget.652 · Cited by 318
mTOR and the control of whole body metabolism
Polak, P., & Hall, M. N. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.01.024 · Cited by 310
Self-citationmTORC1-mediated translational elongation limits intestinal tumour initiation and growth
Faller, W. J., Jackson, T. J., Knight, J. R. P., Ridgway, R. A., Jamieson, T. J., Karim, S. A., Jones, C., Radulescu, S., Huels, D. J., Myant, K., et al. (2014) · Nature · doi:10.1038/nature13896 · Cited by 315
Self-citationmTOR signaling in cellular and organismal energetics
Albert, V., & Hall, M. N. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.12.001 · Cited by 304
Self-citationMetabolic reprogramming, caloric restriction and aging
Anderson, R. M., & Weindruch, R. H. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.11.005 · Cited by 309
“Interestingly, adipose tissue-specific knockout of raptor (component of mTOR Complex I) protects against diet-induced obesity [67].”
The multifaceted role of mTORC1 in the control of lipid metabolism
Ricoult, S. J. H., & Manning, B. D. (2013) · EMBO Reports · doi:10.1038/embor.2013.5 · Cited by 291
Öst, A., Svensson, K., Ruishalme, I., Brännmark, C., Franck, N., Krook, H., Sandström, P., Kjølhede, P., & Strålfors, P. (2010) · Molecular Medicine · doi:10.2119/molmed.2010.00023 · Cited by 274
Emerging Roles for the Lysosome in Lipid Metabolism
Thelen, A. M., & Zoncu, R. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.07.006 · Cited by 275
Kumar, A. T., Lawrence, J. C., Jung, D. Y., Ko, H. J., Keller, S. R., Kim, J. K., Magnuson, M. A., & Harris, T. E. (2010) · Diabetes · doi:10.2337/db09-1061 · Cited by 259
“Rapamycin-mediated inhibition of mTOR has implicated mTORC1 in the regulation of lipolysis (14, 15), however, eliminating mTORC1 by ablating raptor in fat cells does not affect lipolysis (33).”
BackgroundShende, P., Plaisance, I., Morandi, C., Pellieux, C., Berthonneche, C., Zorzato, F., Krishnan, J., Lerch, R. A., Hall, M. N., Rüegg, M. A., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.977066 · Cited by 239
Self-citationInhibition of IL-11 signalling extends mammalian healthspan and lifespan
Widjaja, A. A., Lim, W.-W., Viswanathan, S., Chothani, S., Corden, B., Dasan, C. M., Goh, J. W. T., Lim, R., Singh, B. K., Tan, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07701-9 · Cited by 238
“More detailed study of the vWAT transcriptome revealed that the gene that was most upregulated by anti-IL-11 genome-wide was Ucp1 , which is important for the development of thermogenic ‘beige’ adipocytes in white adipose tissue (WAT) deposits 40,41 (Fig.”
BackgroundMitochondria in the signaling pathways that control longevity and health span
Akbari, M., Kirkwood, T. B. L., & Bohr, V. A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100940 · Cited by 234
“develop obesity and showed improved insulin sensitivity and increased mitochondrial respiration in adipose tissue (Polak et al., 2008).”
BackgroundChakrabarti, P., English, T., Shi, J., Smas, C. M., & Kandror, K. V. (2010) · Diabetes · doi:10.2337/db09-1602 · Cited by 242
“(32) attributed this effect to elevated energy expenditure due to mitochondrial uncoupling.”
BackgroundResultThomanetz, V., Angliker, N., Cloëtta, D., Lustenberger, R. M., Schweighauser, M., Oliveri, F., 昇, 鈴., & Rüegg, M. A. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201205030 · Cited by 233
“The rather weak phenotypes caused by rictor deletion are in stark contrast to the severe phenotypes observed upon deletion of rptor (gene encoding raptor) in the same tissues (Bentzinger et al., 2008; Polak et al., 2008; Gödel et al., 2011).”
Self-citationAMPK–mTOR Signaling and Cellular Adaptations in Hypoxia
Chun, Y., & Kim, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189765 · Cited by 237
Growth and aging: a common molecular mechanism
Blagosklonny, M. V., & Hall, M. N. (2009) · Aging · doi:10.18632/aging.100040 · Cited by 214
“However, the role of mitochondria in life span extension remains elusive, particularly with the recent demonstration that TORC1 in mammalian adipose tissue, like in yeast, negatively controls respiration [26].”
BackgroundSelf-citationResearch progress of mTOR inhibitors
Chen, Y., & Zhou, X. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112820 · Cited by 219
S6K1 Plays a Critical Role in Early Adipocyte Differentiation
Carnevalli, L. S., Masuda, K., Frigerio, F., Bacquer, O. L., Um, S. H., Gandin, V., Topisirović, I., Sonenberg, N., Thomas, G., & Kozma, S. C. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.02.018 · Cited by 212
PTEN in cancer, metabolism, and aging
Ortega-Molina, A., & Serrano, M. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.11.002 · Cited by 207
“This is the case for mice lacking regulatory-associated protein of mTOR (RAPTOR) in adipose tissue, a critical component of the mTORC1 complex, or mice with combined deficiency in ribosomal protein S6 kinases-1 (S6K1) and -2 (S6K2), involved in protein synthesis and cell proliferation and two main downstream effectors…”
BackgroundDuration of Rapamycin Treatment Has Differential Effects on Metabolism in Mice
Fang, Y., Westbrook, R., Hill, C., Boparai, R. K., Arum, O., Spong, A., Wang, F., Javors, M. A., Chen, J., Sun, L. Y., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.008 · Cited by 195
“mice with adipose-specific knockout of Raptor (Polak et al., 2008).”
InfluentialActivation of mTORC1 is essential for β-adrenergic stimulation of adipose browning
Liu, D., Bordicchia, M., Zhang, C., Fang, H., Wei, W., Li, J., Guilherme, A., Guntur, K., Czech, M., & Collins, S. (2016) · Journal of Clinical Investigation · doi:10.1172/jci83532 · Cited by 197
Balanced mTORC1 Activity in Oligodendrocytes Is Required for Accurate CNS Myelination
Lebrun-Julien, F., Bachmann, L. C., Norrmén, C., Trötzmüller, M., Köfeler, H. C., Rüegg, M. A., Hall, M. N., & Suter, U. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1105-14.2014 · Cited by 199
Self-citationRictor/TORC2 Regulates Caenorhabditis elegans Fat Storage, Body Size, and Development through sgk-1
Jones, K. T., Greer, E. R., Pearce, D., & Ashrafi, K. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000060 · Cited by 186
Desjardins, E. M., & Steinberg, G. R. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1049-6 · Cited by 193
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 213
mTOR complex 2 in adipose tissue negatively controls whole-body growth
Cybulski, N., Polak, P., Auwerx, J. H., Rüegg, M. A., & Hall, M. N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811321106 · Cited by 175
“Adipose-specific raptor knockout mice are resistant to diet-induced obesity and have improved glucose metabolism (19).”
BackgroundSelf-citationGong, Q., Hu, Z., Zhang, F., Cui, A., Chen, X., Jiang, H., Gao, J., Chen, X., Han, Y., Liang, Q., et al. (2016) · Hepatology · doi:10.1002/hep.28523 · Cited by 171
Mayoral, R., Osborn, O., McNelis, J., Johnson, A. M., Oh, D. Y., Llorente, C., Chung, H., Li, P., Través, P. G., Bandyopadhyay, G. K., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.02.007 · Cited by 171
mTOR signaling in tumorigenesis
Xu, K. L., Liu, P., & Wei, W. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.10.007 · Cited by 167
“Specifically, the adipose-specific RaptorKOmicehavemuch less adipose tissue, and are less likely to get hyper-cholesterolemia and obesity, which emphasizes the critical role of Raptor and mTORC1 in adipose metabolism and whole body energy homeostasis [39] (Fig.”
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 174
Adipose Organ Development and Remodeling
Cinti, S. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170042 · Cited by 197
Free radicals and male reproduction.
Agarwal, A. K., & Allamaneni, S. S. R. (2011) · PubMed · Cited by 154
Ong, P. S., Wang, L. Z., Dai, X., Tseng, S. H., Loo, S. J., & Sethi, G. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00395 · Cited by 162
“Furthermore, in mice lacking raptor in adipose tissue, an increased insulin sensitivity and resistance to diet-induced obesity were found (Polak et al., 2008).”
BackgroundLoss of mTORC1 signalling impairs β-cell homeostasis and insulin processing
Blandino-Rosano, M., Barbaresso, R., Jiménez-Palomares, M., Bozadjieva-Kramer, N., Werneck‐de‐Castro, J. P., Hatanaka, M., Mirmira, R. G., Sonenberg, N., Liu, M. R., Rüegg, M. A., et al. (2017) · Nature Communications · doi:10.1038/ncomms16014 · Cited by 161
Self-citationBercury, K. K., Dai, J., Sachs, H. H., Ahrendsen, J. T., Wood, T. L., & Macklin, W. B. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4314-13.2014 · Cited by 167
“Furthermore, its activation or downregulation in adipocytes regulates RNA expression for specific lipid synthesis enzymes (Chakrabarti et al., 2010), and adipose-specific knock-out of Raptor results in increased expression of RNAs encoding mitochondrial metabolic proteins (Polak et al., 2008).”
BackgroundA comparative perspective on lipid storage in animals
Birsoy, K., Festuccia, W. T., & Laplante, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.104992 · Cited by 163
“Furthermore, pharmacological or genetic inhibition of mTORC1 is associated with a reduction in adipose tissue mass due to both reduced adipocyte size and number (Polak et al., 2008; Houde et al., 2010).”
BackgroundSansbury, B. E., Cummins, T. D., Tang, Y., Hellmann, J., Holden, C. R., Harbeson, M. A., Chen, Y., Patel, R. P., Spite, M., Bhatnagar, A., et al. (2012) · Circulation Research · doi:10.1161/circresaha.112.266395 · Cited by 156
Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats
Deblon, N., Bourgoin, L., Veyrat‐Durebex, C., Peyrou, M., Vinciguerra, M., Caillon, A., Maeder, C., Fournier, M., Montet, X., Rohner‐Jeanrenaud, F., et al. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01716.x · Cited by 160
“…reported that rapamycin, or deletion of a component of the mTOR complexes, stimulates lipolysis and/or prevents lipogenesis in white adipose cells (Polak et al., 2008; Chakra- Table 2 Plasma TG and NEFA in rats fed a high fat diet Vehicle Vehicle Sirolimus PF Standard diet HF diet HF diet HF…”
BackgroundDifferential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy
Bentzinger, C. F., Lin, S., Romanino, K., Castets, P., Guridi, M., Summermatter, S., Handschin, C., Tintignac, L. A., Hall, M. N., & Rüegg, M. A. (2013) · Skeletal Muscle · doi:10.1186/2044-5040-3-6 · Cited by 153
“This tight feedback control of S6K on IRS1-PKB/Akt was also observed in mice deficient for raptor or mTOR in some tissues including skeletal and heart muscle [16,54-56] but not in others [57].”
Glucose uptake in brown fat cells is dependent on mTOR complex 2–promoted GLUT1 translocation
Olsen, J. M., Sato, M., Dallner, O. S., Sandström, A. L., Pisani, D. F., Chambard, J., Amri, E., Hutchinson, D. S., & Bengtsson, T. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201403080 · Cited by 158
“It is involved in multiple physiological processes such as lipogenesis, lipolysis, and adipogenesis, and has recently been implicated in insulin signaling and sensitivity in white adipose tissue (Polak et al., 2008; Kumar et al., 2010), with a large focus on the role of mTOR in white adipose tissue.”
p62/SQSTM1 at the interface of aging, autophagy, and disease
Bitto, A., Lerner, C. A., Nacarelli, T., Crowe, E. P., Torres, C. A., & Sell, C. (2014) · AGE · doi:10.1007/s11357-014-9626-3 · Cited by 154
Inactivation of mTORC1 in the Developing Brain Causes Microcephaly and Affects Gliogenesis
Cloëtta, D., Thomanetz, V., Baranek, C., Lustenberger, R. M., Lin, S., Oliveri, F., Atanasoski, S., & Rüegg, M. A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3294-12.2013 · Cited by 145
Self-citationIntegration of hormonal and nutrient signals that regulate leptin synthesis and secretion
Lee, M., & Fried, S. K. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90927.2008 · Cited by 144
Pedroso, J. A. B., Zampieri, T. T., & Donato, J. (2015) · Nutrients · doi:10.3390/nu7053914 · Cited by 160
“suggesting that fat deposition may depend on mTORC1 activity [92].”
BackgroundWNT7B Promotes Bone Formation in part through mTORC1
Chen, J., Tu, X., Esen, E., Joeng, K. S., Lin, C., Arbeit, J. M., Rüegg, M. A., Hall, M. N., Ma, L., & Long, F. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004145 · Cited by 141
“3ColI-Cre, Osx-Cre, TetO-Cre, Wnt1-Cre, R26-mT/mG, and Raptor mice are as previously described [21,48,49,50,51,52].”
MethodSelf-citationRecent Advances in Adipose mTOR Signaling and Function: Therapeutic Prospects
Cai, H., Dong, L., & Liu, F. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.11.011 · Cited by 152
“Fat-specific knockout of raptor, a positive regulator of the mTORC1 signaling pathway, had little effect on the expression of PPARg, C/EBP/, and SREBP, despite the lean phenotype of these mice [67].”
BackgroundInfluentialAmino Acid Sensing in Metabolic Homeostasis and Health
Hu, X., & Guo, F. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa026 · Cited by 143
Feedback on Fat: p62-mTORC1-Autophagy Connections
Moscat, J., & Díaz-Meco, M. T. (2011) · Cell · doi:10.1016/j.cell.2011.10.021 · Cited by 146
“In this regard, it is surprising that inhibition of mTORC1 in adipose tissue, by genetic inactivation of raptor, leads to a lean phenotype with resistance to high-fat-dietinduced obesity (Polak et al., 2008).”
BackgroundThe tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissuePreprint
Wada, S., Neinast, M. D., Jang, C., Ibrahim, Y. H., Lee, G., Babu, A., Li, J., Hoshino, A., Rowe, G. C., Rhee, J., et al. (2016) · Genes & Development · doi:10.1101/gad.287953.116 · Cited by 141
“Loss of raptor in fat and portions of the brain leads to browning ofWAT (Polak et al. 2008), while activation ofmTOR in the same tissue distribution via deletion of tuberous sclerosis complex-1 (TSC1) leads to whitening of BAT (Xiang et al. 2015), suggesting that mTOR suppresses adipose browning in…”
BackgroundInfluentialDietary restriction.; mitochondrial function and aging: From yeast to humans
Ruetenik, A., & Barrientos, A. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.005 · Cited by 139
“Similar to what has been observed in yeast tor1 knockouts [19], increased mitochondrial respiration upon TORC1 ablation (raptor KO in adipose tissue) has also been seen in mice [80].”
mTORC1 Controls PNS Myelination along the mTORC1-RXRγ-SREBP-Lipid Biosynthesis Axis in Schwann Cells
Norrmén, C., Figlia, G., Lebrun-Julien, F., Pereira, J. A., Trötzmüller, M., Köfeler, H. C., Rantanen, V., Wessig, C., van Deijk, A. F., Smit, A. B., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.001 · Cited by 143
“To this effect, we crossed mice carrying floxed alleles of raptor and/or rictor (Bentzinger et al., 2008; Polak et al., 2008) with mice expressing Cre-recombinase under control of the Desert hedgehog (Dhh) promoter (Jaegle et al., 2003).”
MethodSelf-citationmTORC1 activates SREBP-2 by suppressing cholesterol trafficking to lysosomes in mammalian cells
Eid, W., Dauner, K., Courtney, K. C., Gagnon, A., Parks, R. J., Sorisky, A., & Zha, X. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705304114 · Cited by 148
“For instance, nutrient-rich conditions activate mTORC1 to increase adipogenesis (2), to up-regulate mitochondrial biogenesis in muscle (1), and to promote hepatic lipogenesis by activating sterol regulatory element-binding proteins (SREBPs) (3), the master transcriptional regulators of lipid and sterol biosynthesis.”
BackgroundmTORC1 is essential for leukemia propagation but not stem cell self-renewal
Hoshii, T., Tadokoro, Y., Naka, K., Ooshio, T., Muraguchi, T., Sugiyama, N., Soga, T., Araki, K., Yamamura, K., & Hirao, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62279 · Cited by 140
“Although mTORC1 has been assumed to function in growth and metabolism of most cell types, previous studies of mice lacking Raptor only in adipocytes or muscle suggest that mTORC1 may have distinct functions in homeostasis depending on the tissue (8, 9).”
TOR‐mediated regulation of metabolism in aging
Antikainen, H., Driscoll, M., Haspel, G., & Dobrowolski, R. (2017) · Aging Cell · doi:10.1111/acel.12689 · Cited by 122
ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling
Winter, J. N., Jefferson, L. S., & Kimball, S. R. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00504.2010 · Cited by 135
“To test whether the ERK and Akt signaling pathways function together to activate mTORC1, cells were treated with maximally effective concentrations of LPA or insulin individually or in combination, and S6K1 phosphorylation on T389, a site directly phosphorylated by mTORC1 (36), was assessed.”
Background
Metadata
- Authors
- Polak, P., Cybulski, N., Feige, J. N., Auwerx, J., Rüegg, M. A., & Hall, M. N.
- Affiliations
- University of Basel (CH)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Hall, Michael N.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 8
- Issue
- 5
- Pages
- 399-410
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2124802842
- Cited by
- 480
- References
- 71
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 17 · 2023: 12 · 2022: 21 · 2021: 23 · 2020: 31 · 2019: 23 · 2018: 26 · 2017: 46 · 2016: 32 · 2015: 35 · 2014: 43 · 2013: 37 · 2012: 38
- FWCI
- 17.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- edoc (University of Basel)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- raptors, mTORC1, white adipose tissue, mitochondrial uncoupling, brown adipose tissue, energy expenditure, diet-induced obesity, hypercholesterolemia, insulin sensitivity
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR, Animals, Adipose Tissue, Brown, Carrier Proteins, Dietary Fats, Energy Metabolism, Hypercholesterolemia, Insulin, Male, Mitochondria, Obesity, Organ Specificity, Proteins, Transcription Factors, Mice, Knockout, Cell Respiration, Sirolimus, 3T3-L1 Cells, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Mice, Adipose Tissue, White, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
