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

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.

Pubmed ID: 21907138


  • Leinninger GM
  • Opland DM
  • Jo YH
  • Faouzi M
  • Christensen L
  • Cappellucci LA
  • Rhodes CJ
  • Gnegy ME
  • Becker JB
  • Pothos EN
  • Seasholtz AF
  • Thompson RC
  • Myers MG


Cell metabolism

Publication Data

September 7, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: P60 DK020541
  • Agency: NIDDK NIH HHS, Id: P60 DK020572
  • Agency: NIDDK NIH HHS, Id: P60 DK020572-34
  • Agency: NIDDK NIH HHS, Id: R01 DK055267
  • Agency: NIDDK NIH HHS, Id: R01 DK057768
  • Agency: NIDDK NIH HHS, Id: R01 DK057768-13
  • Agency: NIDDK NIH HHS, Id: R01 DK078056
  • Agency: NIDDK NIH HHS, Id: R01 DK078056-04
  • Agency: NIDDK NIH HHS, Id: R01 DK078056-05

Mesh Terms

  • Animals
  • Dopamine
  • Electrophysiology
  • Energy Metabolism
  • Gene Expression
  • Gene Knockdown Techniques
  • Hypothalamic Area, Lateral
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Leptin
  • Male
  • Mice
  • Mice, Transgenic
  • Microtomy
  • Motor Activity
  • Neurons
  • Neuropeptides
  • Neurotensin
  • Obesity
  • Receptors, Leptin
  • Ventral Tegmental Area