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Publication : Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons.

First Author  Vong L Year  2011
Journal  Neuron Volume  71
Issue  1 Pages  142-54
PubMed ID  21745644 Mgi Jnum  J:174691
Mgi Id  MGI:5140634 Doi  10.1016/j.neuron.2011.05.028
Citation  Vong L, et al. (2011) Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons. Neuron 71(1):142-54
abstractText  Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part because of incomplete knowledge regarding first-order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first-order neurons. While functionally relevant neurons have been identified, the observed effects have been small, suggesting that most first-order neurons remain unidentified. Here we take an alternative approach and test whether first-order neurons are inhibitory (GABAergic, VGAT(+)) or excitatory (glutamatergic, VGLUT2(+)). Remarkably, the vast majority of leptin's antiobesity effects are mediated by GABAergic neurons; glutamatergic neurons play only a minor role. Leptin, working directly on presynaptic GABAergic neurons, many of which appear not to express AgRP, reduces inhibitory tone to postsynaptic POMC neurons. As POMC neurons prevent obesity, their disinhibition by leptin action on presynaptic GABAergic neurons probably mediates, at least in part, leptin's antiobesity effects.
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