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

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

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Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030.
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030.
Program of Neuroscience, MD Anderson and UTHealth Graduate School for Biological Sciences of the University of Texas Health Science Center at Houston, Houston, TX, 77030.
Department of Psychiatry, Douglas Hospital, McGill University, Montreal, Quebec, Canada, H4H 1R3.


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.


HFD feeding; VMAT2; dopamine; leptin; obesity

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