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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.
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“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]
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“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).”
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“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).”
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“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…”
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
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