VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation

eNeuro. 2017 May 26;4(3):ENEURO.0083-17.2017. doi: 10.1523/ENEURO.0083-17.2017. eCollection 2017 May-Jun.


Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When tested with an intermittent access to HFD where first 2.5-h HFD eating (binge-like) and 24-h HFD feeding were measured, KO mice exhibited more binge-like, but less 24-h HFD feeding. Interestingly, leptin inhibited 24-h HFD feeding in controls but not in KO mice. Thus, VMAT2-mediated neurotransmission from midbrain LepR neurons contributes to both binge-like eating and HFD feeding regulation.

Keywords: HFD feeding; VMAT2; dopamine; leptin; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bulimia / metabolism
  • Bulimia / pathology
  • Diet, High-Fat
  • Disease Models, Animal
  • Disease Susceptibility / metabolism
  • Dopamine / metabolism
  • Feeding Behavior / physiology*
  • Female
  • Glutamic Acid / metabolism
  • Leptin / administration & dosage
  • Leptin / metabolism
  • Male
  • Mesencephalon / cytology
  • Mesencephalon / metabolism*
  • Mesencephalon / pathology
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons / pathology
  • Obesity / metabolism
  • Obesity / pathology
  • Receptors, Leptin / metabolism*
  • Synaptic Transmission / physiology*
  • Tissue Culture Techniques
  • Vesicular Monoamine Transport Proteins / genetics
  • Vesicular Monoamine Transport Proteins / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Leptin
  • Receptors, Leptin
  • Slc18a2 protein, mouse
  • Vesicular Monoamine Transport Proteins
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Dopamine