Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance

Gina M. Leinninger, Darren M. Opland, Young Hwan Jo, Miro Faouzi, Lyndsay Christensen, Laura A. Cappellucci, Christopher J. Rhodes, Margaret E. Gnegy, Jill B. Becker, Emmanuel N. Pothos, Audrey F. Seasholtz, Robert C. Thompson, Martin G. Myers

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189 Scopus citations

Abstract

Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb Nts neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb Nts neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb Nts neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.

Original languageEnglish (US)
Pages (from-to)313-323
Number of pages11
JournalCell metabolism
Volume14
Issue number3
DOIs
StatePublished - Sep 7 2011

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ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Leinninger, G. M., Opland, D. M., Jo, Y. H., Faouzi, M., Christensen, L., Cappellucci, L. A., Rhodes, C. J., Gnegy, M. E., Becker, J. B., Pothos, E. N., Seasholtz, A. F., Thompson, R. C., & Myers, M. G. (2011). Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell metabolism, 14(3), 313-323. https://doi.org/10.1016/j.cmet.2011.06.016