Astrocytic BDNF signaling within the ventromedial hypothalamus regulates energy homeostasis
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) is essential for maintaining energy and glucose balance within the central nervous system. Because the study of its metabolic actions has been limited to effects in neuronal cells, its role in other cell types within the brain remains poorly understood. Here we show that astrocytic BDNF signaling within the ventromedial hypothalamus (VMH) modulates neuronal activity in response to changes in energy status. This occurs via the truncated TrkB.T1 receptor. Accordingly, either fasting or central BDNF depletion enhances astrocytic synaptic glutamate clearance, thereby decreasing neuronal activity in mice. Notably, selective depletion of TrkB.T1 in VMH astrocytes blunts the effects of energy status on excitatory transmission, as well as on responses to leptin, glucose and lipids. These effects are driven by increased astrocytic invasion of excitatory synapses, enhanced glutamate reuptake and decreased neuronal activity. We thus identify BDNF/TrkB.T1 signaling in VMH astrocytes as an essential mechanism that participates in energy and glucose homeostasis.
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BDNF can significantly enhance the electrical activity of neurons in the VMH, thereby altering energy homeostasis.
“It has been confirmed that BDNF can significantly enhance the electrical activity of neurons in the VMH [47], thereby altering energy homeostasis.”
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- Authors
- Ameroso, D., Meng, A., Chen, S., Felsted, J., Dulla, C. G., & Rios, M.
- Affiliations
- Tufts University (US)
- Corresponding author
- Rios, Maribel
- Venue
- Nature Metabolism
- Published
- 2022-05-02
- Volume
- 4
- Issue
- 5
- Pages
- 627-643
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC9177635
- OpenAlex
- W4225287891
- Cited by
- 67
- References
- 66
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 22 · 2023: 10 · 2022: 9
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK117935, F31DK118789, T32DK124170)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (1R21NS091871, 5T32NS061764)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- brain-derived neurotrophic factor, astrocytes, ventromedial hypothalamus, energy homeostasis, glucose homeostasis, glutamate clearance, excitatory synapses, neuronal activity, fasting, leptin, lipids
- MeSH terms
- Animals, Astrocytes, Glucose, Glutamates, Homeostasis, Hypothalamus, Brain-Derived Neurotrophic Factor, Mice
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