Location: Children's Nutrition Research CenterTitle: VMAT2-mediated neurotransmission from midbrain leptin receptor neurons in feeding regulation
|XU, YUANZHONG - University Of Texas Health Science Center|
|LU, YUNGANG - University Of Texas Health Science Center|
|XU, PINGWEN - Children'S Nutrition Research Center (CNRC)|
|MANGIERI, LEANDRA - University Of Texas Health Science Center|
|ISINGRINI, ELSA - McGill University - Canada|
|XU, YONG - Children'S Nutrition Research Center (CNRC)|
|GIROS, BRUNO - McGill University - Canada|
|TONG, QINGCHUN - University Of Texas Health Science Center|
Submitted to: eNeuro
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/10/2017
Publication Date: 5/16/2017
Citation: Xu, Y., Lu, Y., Xu, P., Mangieri, L., Isingrini, E., Xu, Y., Giros, B., Tong, Q. 2017. VMAT2-mediated neurotransmission from midbrain leptin receptor neurons in feeding regulation. eNeuro. 4(3):1-15. doi:10.1523/ENEURO.0083-17.2017.
Interpretive Summary: Obesity is a serious global health problem. Leptin is a hormone that inhibits food intake and decreases body weight. Here we showed that the effects of leptin on food intake are mediated by a brain molecule, namely VMAT2. These findings suggest that VMAT2 could be a potential target for treatment of obesity.
Technical Abstract: 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 (knockout [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.