Evidence map›Paper›PMID 40770666›Full record

ArticleBiology of sex differences2025

Lack of glutamate neurotransmission in melanin-concentrating hormone neurons alters mouse reproduction and metabolism in a sex-specific manner.

Bethany G Beekly, Dania Zeidan, Wenicios F Chaves, Jonah-Isabella Sta-Monica, Thomas Saunders, Cristina Saenz de Miera, Christian R Burgess, Carol F Elias

Abstract read
In one paragraph

Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Bethany G BeeklyDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Dania ZeidanDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Wenicios F ChavesDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Jonah-Isabella Sta-MonicaDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Thomas SaundersDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Cristina Saenz de MieraDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Christian R BurgessDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Carol F EliasDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. cfelias@umich.edu.

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Metabolic Phenotyping in Live Models of Obesity and DiabetesU2CDK135066 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Nathan R. Qi · 2023 to 2026
$3.5M
Elucidating the role for MCH neurons in feeding behavior and responses to sensory food cuesR01DK129366 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BURGESS, CHRISTIAN RICHARD · 2021 to 2025
$2.1M
Sex-specific role of androgen signaling in neuroendocrine-behavior interfaceR01HD106962 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carol Fuzeti Elias · 2023 to 2026
$1.7M
Prenatal photoperiod action in hypothalamic developmentR21HD109485 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELIAS, CAROL FUZETI · 2022 to 2023
$429k
MCH neurons: the potential link between sleep and the neuroendocrine functionR21HD090567 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELIAS, CAROL FUZETI, VANINI, GIANCARLO · 2017 to 2018
$428k
Role of Melanin-concentrating Hormone in the Integration of Sleep and Reproductive PhysiologyF31HD102160 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BEEKLY, BETHANY GENELLE · 2020 to 2022
$112k
Fundação de Amparo à Pesquisa do Estado de São Paulo 2020/06661-2 and 2023/02027-5National Institute of Child Health and Human Development HD102160National Institute of Child Health and Human Development HD106962National Institute of Child Health and Human Development HD109485NICHD NIH HHS F31 HD102160NICHD NIH HHS R01 HD106962NICHD NIH HHS R21 HD090567NICHD NIH HHS R21 HD109485NIDDK NIH HHS DK129366NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK129366NIDDK NIH HHS U2C DK135066
6 · The paper itself

Abstract

backgroundMelanin-concentrating hormone (MCH) neurons contribute to the regulation of a diverse array of physiological functions including glucose and energy homeostasis. MCH neurons express genes involved in the synthesis, packaging, and release of glutamate, the brain’s predominant excitatory neurotransmitter. Deletion of vesicular glutamate transporter 2 (VGLUT2, Slc17a6 gene) in MCH neurons of male mice results in a hypophagic, hyperactive, lean phenotype. However, the metabolic and reproductive effects of VGLUT2 deletion in females have not been fully addressed.

methodsPrevious studies have utilized Pmch-Cre mice generated using a bacterial artificial chromosome (BAC). The loci of insertion for the BAC are random and may fail to recapitulate epigenetic regulation at the native gene locus. Here, we generated a novel knock-in Pmch-iCre mouse model and investigated the effects of deleting Slc17a6 from MCH neurons in both male and female mice. Assessment of sexual maturation, fertility, glucose homeostasis and energy balance (food intake, body composition, energy expenditure, locomotion, glucose and fat oxidation) on regular chow and high fat diet (HFD) were performed in both sexes.

resultsLack of glutamate neurotransmission in MCH neurons (PmchΔVglut2 mice) delays puberty onset and completion in female, but not male mice. PmchΔVglut2 females were also protected against (HFD)-induced disruption of estrous cycles. On a regular chow diet, neither male nor female PmchΔVglut2 mice showed differences in body weight, food intake, or lean and fat masses compared to littermate controls until 20 weeks of age. At 24 weeks of age, PmchΔVglut2 females exhibited reduced total body mass, and males had lower fat mass. PmchΔVglut2 female mice also gained less weight on HFD than littermate controls. An attenuation of HFD-induced disruption of daily feeding pattern was observed in PmchΔVglut2 mice of both sexes, while only males were protected against insulin resistance on HFD.

conclusionsGlutamate neurotransmission from MCH neurons has a sex-specific role in sexual maturation, fertility, typical weight gain trajectory, and HFD-induced weight gain and insulin resistance. In addition, a sex-independent role in daily feeding pattern was observed.

Indexed as

Glutamic AcidHypothalamic HormonesMelaninsNeuronsPituitary HormonesReproductionSex CharacteristicsSynaptic TransmissionVesicular Glutamate Transport Protein 2AnimalsEnergy MetabolismFemaleMaleMiceSexual MaturationGlutamic AcidHypothalamic Hormonesmelanin-concentrating hormoneMelaninsPituitary HormonesSlc17a6 protein, mouseVesicular Glutamate Transport Protein 2Energy homeostasisGlucose toleranceLateral hypothalamusMetabolismPubertyReproduction

Identifiers

PMID40770666
PMCPMC12326619

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.