Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding

Jonathan Hommel, Richard Trinko, Robert M. Sears, Dan Georgescu, Zong Wu Liu, Xiao Bing Gao, Jeremy J. Thurmon, Michela Marinelli, Ralph J. DiLeone

Research output: Contribution to journalArticle

601 Citations (Scopus)

Abstract

The leptin hormone is critical for normal food intake and metabolism. While leptin receptor (Lepr) function has been well studied in the hypothalamus, the functional relevance of Lepr expression in the ventral tegmental area (VTA) has not been investigated. The VTA contains dopamine neurons that are important in modulating motivated behavior, addiction, and reward. Here, we show that VTA dopamine neurons express Lepr mRNA and respond to leptin with activation of an intracellular JAK-STAT pathway and a reduction in firing rate. Direct administration of leptin to the VTA caused decreased food intake while long-term RNAi-mediated knockdown of Lepr in the VTA led to increased food intake, locomotor activity, and sensitivity to highly palatable food. These data support a critical role for VTA Lepr in regulating feeding behavior and provide functional evidence for direct action of a peripheral metabolic signal on VTA dopamine neurons.

Original languageEnglish (US)
Pages (from-to)801-810
Number of pages10
JournalNeuron
Volume51
Issue number6
DOIs
StatePublished - Sep 21 2006
Externally publishedYes

Fingerprint

Leptin Receptors
Ventral Tegmental Area
Dopaminergic Neurons
Mesencephalon
Leptin
Eating
Feeding Behavior
Locomotion
RNA Interference
Reward
Hypothalamus
Hormones
Food
Messenger RNA

Keywords

  • HUMDISEASE
  • SIGNALING
  • SYSNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hommel, J., Trinko, R., Sears, R. M., Georgescu, D., Liu, Z. W., Gao, X. B., ... DiLeone, R. J. (2006). Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding. Neuron, 51(6), 801-810. https://doi.org/10.1016/j.neuron.2006.08.023

Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding. / Hommel, Jonathan; Trinko, Richard; Sears, Robert M.; Georgescu, Dan; Liu, Zong Wu; Gao, Xiao Bing; Thurmon, Jeremy J.; Marinelli, Michela; DiLeone, Ralph J.

In: Neuron, Vol. 51, No. 6, 21.09.2006, p. 801-810.

Research output: Contribution to journalArticle

Hommel, J, Trinko, R, Sears, RM, Georgescu, D, Liu, ZW, Gao, XB, Thurmon, JJ, Marinelli, M & DiLeone, RJ 2006, 'Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding', Neuron, vol. 51, no. 6, pp. 801-810. https://doi.org/10.1016/j.neuron.2006.08.023
Hommel J, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB et al. Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding. Neuron. 2006 Sep 21;51(6):801-810. https://doi.org/10.1016/j.neuron.2006.08.023
Hommel, Jonathan ; Trinko, Richard ; Sears, Robert M. ; Georgescu, Dan ; Liu, Zong Wu ; Gao, Xiao Bing ; Thurmon, Jeremy J. ; Marinelli, Michela ; DiLeone, Ralph J. / Leptin Receptor Signaling in Midbrain Dopamine Neurons Regulates Feeding. In: Neuron. 2006 ; Vol. 51, No. 6. pp. 801-810.
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