Cited by 480Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and Cancer

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Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration

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Polak, Pazit, Cybulski, Nadine, Feige, Jerome N., Auwerx, Johan, Rüegg, Markus A., Hall, Michael N.·2008·Cell Metabolism

DOI 10.1016/j.cmet.2008.09.003

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Abstract

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.

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Background
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Cysteine‐rich protein 61 regulates adipocyte differentiation from mesenchymal stem cells through mammalian target of rapamycin complex 1 and canonical Wnt signaling
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“Mice with adipose-specific knockout of raptor are lean, resistant to diet-induced obesity, and demonstrate an increase in mitochondrial uncoupling in white adipose tissue (Polak et al. 2008).”
Background
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“Such estimations shed light on the binding affinity between proteins and ligands, revealing shifts in thermodynamics when these molecules bind (Polak et al., 2008).”
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“Accordingly, mice with adipose-specific knockout of the Raptor component of mTORC1 are lean, resistant to diet-induced obesity (Polak et al., 2008) and display improved glucose tolerance and insulin sensitivity.”
Background
Vascular effects of disrupting endothelial mTORC1 signaling in obesity
Reho, J. J., Guo, D., Beyer, A., Wegman‐Points, L., Pierce, G. L., & Rahmouni, K. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00113.2021 · Cited by 10
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“Rptor and Rctor mice (72) were provided by Michael Hall (University of Basel).”
Method
Tissue-restricted inhibition of mTOR using chemical genetics
Wassarman, D. R., Bankapalli, K., Pallanck, L. J., & Shokat, K. M. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2204083119 · Cited by 7
“Genetic disruption of the mTOR pathway in skeletal muscle causes insulin resistance in mice (8), but disruption in adipose increases insulin sensitivity (9).”
Background
Regulatory-Associated Protein of mTOR-Mediated Signaling: A Nexus Between Tumorigenesis and Disease
Chouhan, S., Kumar, A., Piprode, V., Dasgupta, A., Singh, S., & Khalique, A. (2024) · Targets · doi:10.3390/targets2040020 · Cited by 10
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BMP11 regulates thermogenesis in white and brown adipocytes
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BackgroundInfluential
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Li, X., Morel, J., Masi, A. D., Lalou, A., Sulc, J., Benegiamo, G., Poisson, J., Liu, Y. J., von Alvensleben, G., Maxime, N., et al. (2024) · Cell Systems · doi:10.1016/j.cels.2024.05.006 · Cited by 9
Self-citation
Differential metabolic sensitivity of insulin-like-response- and TORC1-dependent overgrowth inDrosophilafat cells
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Role of Branched-Chain Amino Acid Catabolism in the Regulation of Adipocyte Metabolism
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Deletion of Rptor in Preosteoblasts Reveals a Role for the Mammalian Target of Rapamycin Complex 1 ( mTORC1) Complex in Dietary‐Induced Changes to Bone Mass and Glucose Homeostasis in Female Mice
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“In contrast, mice with deletion of Rptor in WAT suffer from severe hepatic steatosis despite being protected against dietinduced obesity (via increased energy expenditure).((80,81)) Similarly, inactivation of mTORC1 in skeletal muscle causes resistance to HFD-induced metabolic dysfunction and improved glucose toleranc…”
Background
Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9
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Background
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice
Tang, F., Zhang, P., Ye, P., Lazarski, C. A., Wu, Q., Bergin, I. L., Bender, T. P., Hall, M. N., Cui, Y., Zhang, L., et al. (2017) · eLife · doi:10.7554/elife.32497 · Cited by 7
“…As germline deletion of Rptor (which encode the Raptor protein) is embryonic-lethal, we crossed mice harboring homozygous loxp-flanked Rptor exon 6 (Polak et al., 2008) to those with interferoninducible Mx1-Cre recombinase transgene, which allows inducible deletion of target genes effectively in…”
BackgroundSelf-citation
Regulatory Mechanism of mTOR Signaling Pathway on Cell Energy Metabolism
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Self-citation
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Is the secret for a successful aging to keep track of cancer pathways?
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Background
Adipose tissue browning: mTOR branches out
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Seasonal effects of the UCP3 and the RPTOR gene polymorphisms on obesity traits in Japanese adults
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Glucose Metabolism, Insulin, and Aging
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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.
ORCID: Polak, Pazit
Auwerx, Johan
Rüegg, Markus A.
Hall, Michael N.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2008-11
Volume: 8
Issue: 5
Pages: 399-410
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2008.09.003
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1719 d)
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

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Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration

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