Dataset Information

Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons.

ABSTRACT:

Objectives

Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons.

Methods

MCH neurons were profiled using Cre-dependent molecular profiling technologies (vTRAP). MCHCre mice crossed to Vglut2^fl/flmice or to DTR^fl/flwere used to identify the role of glutamate in MCH neurons. We assessed metabolic parameters such as body composition, glucose tolerance, or sucrose preference.

Results

We found that nearly all MCH neurons in the LH are glutamatergic and that a loss of glutamatergic signaling from MCH neurons from a glutamate transporter (VGlut2) knockout leads to a reduced weight, hypophagia and hyperkinetic behavior with improved glucose tolerance and a loss of sucrose preference. These effects are indistinguishable from those seen after ablation of MCH neurons. These findings are in contrast to those seen in mice with a knockout of the MCH neuropeptide, which show normal glucose preference and do not have improved glucose tolerance.

Conclusions

Overall, these data show that the vast majority of MCH neurons are glutamatergic, and that glutamate and MCH signaling mediate partially overlapping functions by these neurons, presumably by activating partially overlapping postsynaptic populations. The diverse functional effects of MCH neurons are thus mediated by a composite of glutamate and MCH signaling.

SUBMITTER: Schneeberger M

PROVIDER: S-EPMC6026325 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons.

Schneeberger Marc M Tan Keith K Nectow Alexander R AR Parolari Luca L Caglar Caner C Azevedo Estefania E Li Zhiying Z Domingos Ana A Friedman Jeffrey M JM

Molecular metabolism 20180508

<h4>Objectives</h4>Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons.<h4>Methods</h4>MCH neurons were profiled using Cre-dependent molecular profiling technologies (vTRAP). MCHCre mice crossed to Vglut2<sup>fl/fl</sup>mice or to DTR<sup>fl/fl</sup>were use ...[more]

PMID: 29843980

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Dataset Information

Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons.

Objectives

Methods

Results

Conclusions

Publications

Functional analysis reveals differential effects of glutamate and MCH neuropeptide in MCH neurons.

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