Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons
By Linh Vong, C. Ye, Zongfang Yang, Brian J. Choi, S. Chua, Bradford B. Lowell. Neuron, 2011
1,163 citations recorded by the source corpus.
SUMMARY Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part due to 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 anti-obesity 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 likely mediates, at least in part, leptin’s anti-obesity effects.
Subfields: Endocrine and Autonomic Systems, Nutrition and Dietetics, Physiology
View Paper: https://www.semanticscholar.org/paper/55dd92243724aa77ec40d69e4fab6f9559692cd9
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In Endocrine and Autonomic Systems
In Nutrition and Dietetics
In Physiology
Citations in the corpus
- The basal interstitial nucleus (BIN) of the cerebellum provides diffuse ascending inhibitory input to the floccular granule cell layer (2018, methodology): “Lowell (Vong et al., 2011), were obtained from Jackson Laboratories (JAX#016963, Table 1), and maintained as homozygotes in the Erasmus MC animal core facility.”
- Activation of VTA GABA neurons disrupts reward consumption (2012, positive): “Results Optogenetic stimulation of VTA GABA neurons To selectively stimulate VTA GABA neurons, we injected a Cre-inducible adeno-associated viral construct, coding for ChR2-eYFP or eGFP (Tsai et al., 2009) unilaterally into the VTA of adult VGat-ires-Cre mice (Vong et al., 2011).”
- Neuron-type specific signals for reward and punishment in the ventral tegmental area (2012, methodology): “and six adult male mice, backcrossed with C57/BL6J mice, heterozygous for Cre recombinase under the control of the Vgat gene ( Vgat -ires-Cre”
- Whole-brain mapping of direct inputs to midbrain dopamine neurons. (2012, positive): “) and Vgat-ires-Cre (Vong et al., 2011) lines were backcrossed with C57BL6.”