Increased Expression of Transthyretin in Leptin-Deficient ob/ob Mice is not Causative for Their Major Phenotypic Abnormalities

Authors

  • C. Rendenbach,

    1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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    • These authors contributed equally to this study.
  • S. Ganswindt,

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    • These authors contributed equally to this study.
  • S. Seitz,

    1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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    • These authors contributed equally to this study.
  • F. Barvencik,

    1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • A. K. Huebner,

    1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • A. Baranowsky,

    1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • T. Streichert,

    1. Department of Clinical Chemistry/Clinical Laboratories, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • A. Niemeier,

    1. Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    2. Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • J. Heeren,

    1. Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • M. Amling,

    1. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • A. Bartelt,

    Corresponding author
    1. Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    2. Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    • Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • T. Schinke

    Corresponding author
    • Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Correspondences to: Alexander Bartelt, Departments of Biochemistry and Molecular Cell Biology and Orthopedics, University Medical Center Hamburg Eppendorf, Martinistrasse 52, Hamburg 20246, Germany (e-mail: abartelt@uke.uni-hamburg.de).

Thorsten Schinke, Department of Osteology and Biomechanics, University Medical Center Hamburg Eppendorf, Martinistrasse 52, Hamburg 20246, Germany (e-mail: schinke@uke.uni-hamburg.de).

Abstract

The hormone leptin is a critical regulator of adipogenesis and energy metabolism. Similarly, leptin-deficient ob/ob mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass. By genome-wide expression analysis using hypothalamus RNA from wild-type and ob/ob mice, we observed the increased expression of the gene for transthyretin (Ttr) in the latter, as confirmed by quantitative real-time-polymerase chain reaction. Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob/ob mice, we investigated whether the additional absence of Ttr would influence the ob/ob phenotype. It was found that Ttr-deficient ob/ob mice were indistinguishable from ob/ob littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels. Although all of these parameters were identical to wild-type controls in Ttr-deficient mice, we found that the sole deletion of Ttr caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue. Interestingly, all these latter parameters were highest in Ttr-deficient ob/ob mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age. Taken together, our data demonstrate that the increased expression of Ttr in ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities.

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