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Ablation of Neurons Expressing Melanin-Concentrating Hormone (MCH) in Adult Mice Improves Glucose Tolerance Independent of MCH Signaling

2013; Society for Neuroscience; Volume: 33; Issue: 5 Linguagem: Inglês

10.1523/jneurosci.3921-12.2013

1529-2401

Benjamin B. Whiddon, Richard D. Palmiter,

Adipose Tissue and Metabolism

Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine–amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo , we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH ( Pmch ). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch DTR /+ mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.