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

Biozentrum, University of Basel, Basel, CH-4056, Switzerland.
Cell metabolism (Impact Factor: 17.57). 12/2008; 8(5):399-410. DOI: 10.1016/j.cmet.2008.09.003
Source: PubMed


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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    • "Mice Mutant mice were obtained by crossing mice with floxed alleles of raptor and/ or rictor (Bentzinger et al., 2008; Polak et al., 2008) with mice expressing Cre under the Dhh promoter (Jaegle et al., 2003). Littermates lacking Cre were used as controls. "
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    Cell Reports 10/2014; 9(2). DOI:10.1016/j.celrep.2014.09.001 · 8.36 Impact Factor
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    • "However, similar to acute rapamycin treatment, abrogation of mTORC1 activity by raptor deletion increases p-Akt in muscle cells and skeletal muscle [22,38]. Moreover, deletion of raptor in adipose tissue protects mice from high fat diet induced weight gain and improves their glucose tolerance [41]. This indicates that inhibited mTORC1 signaling by AZD8055 likely does not account for the metabolic effects observed by AZD8055. "
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    Molecular Metabolism 09/2014; DOI:10.1016/j.molmet.2014.06.004
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    • "Global deletion of mTOR or Raptor in the mouse leads to early postimplantation lethality (Gangloff et al., 2004; Guertin et al., 2006; Murakami et al., 2004). Subsequent tissue-specific knockout studies have identified crucial roles for mTORC1 in several tissues, but its function in skeletal development has not been examined genetically (Bentzinger et al., 2008; Polak et al., 2008; Yilmaz et al., 2012). Here, through deletion of either mTOR or Raptor, we demonstrate that mTORC1 signaling is required for optimal protein production in chondrocytes, thus controlling cell size, the amount of cartilage matrix and, ultimately, skeletal size. "
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