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

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

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407 Scopus citations

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 (raptorad-/-). Compared to control littermates, raptorad-/- 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 raptorad-/- mice displayed enhanced expression of genes encoding mitochondrial uncoupling proteins characteristic of brown fat. Leanness of the raptorad-/- 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.

Original languageEnglish
Pages (from-to)399-410
Number of pages12
JournalCell Metabolism
Volume8
Issue number5
DOIs
StatePublished - 5 Nov 2008
Externally publishedYes

Bibliographical note

Funding Information:
We thank K. Beier and I. Ginez for assistance with histological analysis; T. Harach for assistance with the glucose tolerance test; A. Hein and P. Demougin for help with qPCR; J. Zoll, A.L. Lang, and B. Geny for valuable discussions and technical assistance with Clark electrode measurements; A. Löschmann for technical assistance with genotyping and histology; and T. Sorg, X. Warot, and M.F. Champy for contributions to generation and phenotyping of knockout mice. We thank K. Thomas and members of the Hall, Rüegg, and Auwerx groups for helpful discussions. We acknowledge support from the Roche Research Foundation (P.P.), FEBS (J.N.F.), and the Swiss National Science Foundation and the Canton of Basel (M.A.R. and M.N.H.). We declare that no competing interests exist.

Funding

We thank K. Beier and I. Ginez for assistance with histological analysis; T. Harach for assistance with the glucose tolerance test; A. Hein and P. Demougin for help with qPCR; J. Zoll, A.L. Lang, and B. Geny for valuable discussions and technical assistance with Clark electrode measurements; A. Löschmann for technical assistance with genotyping and histology; and T. Sorg, X. Warot, and M.F. Champy for contributions to generation and phenotyping of knockout mice. We thank K. Thomas and members of the Hall, Rüegg, and Auwerx groups for helpful discussions. We acknowledge support from the Roche Research Foundation (P.P.), FEBS (J.N.F.), and the Swiss National Science Foundation and the Canton of Basel (M.A.R. and M.N.H.). We declare that no competing interests exist.

FundersFunder number
Canton of Basel
Roche Research Foundation
Federation of European Biochemical Societies
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

    Keywords

    • HUMDISEASE
    • SIGNALING

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