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Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance

Abstract

The physiologic importance of GABAergic neurotransmission in hypothalamic neurocircuits is unknown. To examine the importance of GABA release from agouti-related protein (AgRP) neurons (which also release AgRP and neuropeptide Y), we generated mice with an AgRP neuron–specific deletion of vesicular GABA transporter. These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance.

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Figure 1: Generation of mice lacking GABA release from AgRP neurons.
Figure 2: Energy homeostasis in Agrp-Ires-cre; Vgatflox/flox mice.
Figure 3: Ghrelin-induced food intake in Vgatflox/flox mice and Agrp-Ires-cre; Vgatflox/flox mice.

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Acknowledgements

This work was supported by US National Institutes of Health grants (RO1 DK071051 and PO1 DK56116 to B.B.L.; RO1 DK071320, RO1 DK53301 and PO1 DK56116 to J.K.E.) and the Beth Israel Deaconess Medical Center Transgenic Facility, which is supported by the Boston Obesity Nutrition Research Center (P30 DK046200) and the Boston Area Diabetes Endocrinology Research Center (P30 DK057521). Q.T. is the recipient of a Pilot and Feasibility Award from the US National Institutes of Health–funded Boston Obesity Nutrition Research Center (P30 DK046200) and a Young Investigator Award from the North American Association for the Study of Obesity.

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Contributions

Q.T. and B.B.L. conceived and designed the experiments. Q.T. generated the Vgatflox/flox mice and conducted the experiments. J.E.J. generated the Agrp-Ires-cre mice. C.-P.Y. carried out the electrophysiological recording studies. Q.T. and B.B.L. wrote the paper. J.K.E. provided guidance for many aspects of this study. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Bradford B Lowell.

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Supplementary Figures 1–3 and Supplementary Methods (PDF 1121 kb)

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Tong, Q., Ye, CP., Jones, J. et al. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci 11, 998–1000 (2008). https://doi.org/10.1038/nn.2167

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