ArticleProceedings of the National Academy of Sciences of the United States of America2020
Essential and sex-specific effects of mGluR5 in ventromedial hypothalamus regulating estrogen signaling and glucose balance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Hypothalamic actions of estrogens in the regulation of energy and glucose homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- Spatially convergent functional MRI signatures of diabetes and male sex identify genetic vulnerabilities to accelerated brain ageing.Brain communications · 2026Article
- Membrane-associated estrogen receptor α prevents the amyloid β-induced suppression of GIRK channel activity in hippocampal neurons from female mice.Biology of sex differences · 2025Article
- Inhibition of metabotropic glutamate receptor-5 alleviates hepatic steatosis by enhancing autophagyWorld journal of gastroenterology · 2025Article
- Hypothalamic Estrogen Receptor α Is Essential for Female Marmoset Sexual Behavior Without Protecting From Obesity.Journal of the Endocrine Society · 2025Article
- Central and peripheral neural circuits regulating glucose homeostasis.npj biomedical innovations · 2025Review
- Sex differences in ketogenic diet: are men more likely than women to lose weight?Frontiers in nutrition · 2025Review
- Hypothalamic GABAergic neurons: their roles in health and metabolic diseases.Frontiers in endocrinology · 2025Review
- Parvalbumin interneuron mGluNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Loss of mGluMolecular psychiatry · 2024Article
- Female-specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and estrogen receptor α.Cell reports · 2024Article
- The Role of BDNF and TrkB in the Central Control of Energy and Glucose Balance: An Update.Biomolecules · 2024Review
- Parvalbumin interneuron mGlubioRxiv : the preprint server for biology · 2024Article
- The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause.Frontiers in endocrinology · 2024Review
- mGluR5 in Astrocytes in the Ventromedial Hypothalamus Regulates Pituitary Adenylate Cyclase-Activating Polypeptide Neurons and Glucose Homeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.International review of neurobiology · 2023Review
- Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.Science advances · 2022Article
- The ventromedial hypothalamic nucleus: watchdog of whole-body glucose homeostasis.Cell & bioscience · 2022Review
- Astrocytic BDNF signaling within the ventromedial hypothalamus regulates energy homeostasis.Nature metabolism · 2022Article
- The Case for Clinical Trials with Novel GABAergic Drugs in Diabetes Mellitus and Obesity.Life (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The ventromedial hypothalamus (VMH) plays chief roles regulating energy and glucose homeostasis and is sexually dimorphic. We discovered that expression of metabotropic glutamate receptor subtype 5 (mGluR5) in the VMH is regulated by caloric status in normal mice and reduced in brain-derived neurotrophic factor (BDNF) mutants, which are severely obese and have diminished glucose balance control. These findings led us to investigate whether mGluR5 might act downstream of BDNF to critically regulate VMH neuronal activity and metabolic function. We found that mGluR5 depletion in VMH SF1 neurons did not affect energy balance regulation. However, it significantly impaired insulin sensitivity, glycemic control, lipid metabolism, and sympathetic output in females but not in males. These sex-specific deficits are linked to reductions in intrinsic excitability and firing rate of SF1 neurons. Abnormal excitatory and inhibitory synapse assembly and elevated expression of the GABAergic synthetic enzyme GAD67 also cooperate to decrease and potentiate the synaptic excitatory and inhibitory tone onto mutant SF1 neurons, respectively. Notably, these alterations arise from disrupted functional interactions of mGluR5 with estrogen receptors that switch the normally positive effects of estrogen on SF1 neuronal activity and glucose balance control to paradoxical and detrimental. The collective data inform an essential central mechanism regulating metabolic function in females and underlying the protective effects of estrogen against metabolic disease.
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Registered trials
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