Leptin targets in the mouse brain

Michael M. Scott, Jennifer L. Lachey, Scott M. Sternson, Charlotte E. Lee, Carol F. Elias, Jeffrey M. Friedman, Joel K. Elmquist

Research output: Contribution to journalArticle

296 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)518-532
Number of pages15
JournalJournal of Comparative Neurology
Volume514
Issue number5
DOIs
StatePublished - Jun 10 2009

Keywords

  • CNS distribution
  • Cre recombinase
  • Green fluorescent protein
  • In situ hybridization histochemistry
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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    Scott, M. M., Lachey, J. L., Sternson, S. M., Lee, C. E., Elias, C. F., Friedman, J. M., & Elmquist, J. K. (2009). Leptin targets in the mouse brain. Journal of Comparative Neurology, 514(5), 518-532. https://doi.org/10.1002/cne.22025