Leptin targets in the mouse brain

Authors

  • Michael M. Scott,

    1. Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
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    • The first two authors contributed equally.

  • Jennifer L. Lachey,

    1. Acceleron Pharmaceuticals, Cambridge, Massachusetts 02139
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    • The first two authors contributed equally.

  • Scott M. Sternson,

    1. Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
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  • Charlotte E. Lee,

    1. Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
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  • Carol F. Elias,

    1. Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
    2. Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-900 Brazil
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  • Jeffrey M. Friedman,

    Corresponding author
    1. Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
    • Box 305, Howard Hughes Medical Institute, Rockefeller University, 1230 York Ave., New York, NY 10021
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  • Joel K. Elmquist

    1. Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
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Abstract

The central actions of leptin are essential for homeostatic control of adipose tissue mass, glucose metabolism, and many autonomic and neuroendocrine systems. In the brain, leptin acts on numerous different cell types via the long-form leptin receptor (LepRb) to elicit its effects. The precise identification of leptin's cellular targets is fundamental to understanding the mechanism of its pleiotropic central actions. We have systematically characterized LepRb distribution in the mouse brain using in situ hybridization in wildtype mice as well as by EYFP immunoreactivity in a novel LepRb-IRES-Cre EYFP reporter mouse line showing high levels of LepRb mRNA/EYFP coexpression. We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex. Expression in insular cortex, lateral septal nucleus, medial preoptic area, rostral linear nucleus, and in the Edinger-Westphal nucleus was also observed and had been previously unreported. The LepRb-IRES-Cre reporter line was used to chemically characterize a population of leptin receptor-expressing neurons in the midbrain. Tyrosine hydroxylase and Cre reporter were found to be coexpressed in the ventral tegmental area and in other midbrain dopaminergic neurons. Lastly, the LepRb-IRES-Cre reporter line was used to map the extent of peripheral leptin sensing by central nervous system (CNS) LepRb neurons. Thus, we provide data supporting the use of the LepRb-IRES-Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor. J. Comp. Neurol. 514:518–532, 2009. © 2009 Wiley-Liss, Inc.

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