Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance.
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.
Tong
Qingchun
Q
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Ave., Boston, Massachusetts 02215, USA.
Ye
Chian-Ping
CP
Jones
Juli E
JE
Elmquist
Joel K
JK
Lowell
Bradford B
BB
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D015502:Absorptiometry, Photon / Q000379:methods; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D054439:Ghrelin / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D018408:Patch-Clamp Techniques; D012737:Sex Factors; D013569:Synapses / Q000378:metabolism*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D054369:Agouti-Related Protein; D018691:Excitatory Amino Acid Antagonists; D054439:Ghrelin; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate