Brain-Derived Neurotrophic Factor/Tropomyosin-Related Kinase Receptor Type B Signaling Is a Downstream Effector of the Brainstem Melanocortin System in Food Intake Control
Abstract
It has been shown that the neurotropin brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor type B (TrkB), contribute to the central control of food intake. BDNF has previously been implicated as a probable downstream effector of melanocortinergic signaling within the ventromedial hypothalamus, and we have shown its implication as an anorexigenic factor within the brainstem autonomic integrator of food intake control, namely the dorsal vagal complex (DVC). In the brainstem, the melanocortinergic signaling pathway is known to integrate phasic responses to satiety signals, such as cholecystokinin. In this study, we explored the interactions between melanocortin and BDNF/TrkB signaling within the DVC. First, we tested the effect of a local pharmacological activation or inhibition of melanocortin receptors type 3/4 (MC3/4R) on BDNF protein content in the DVC of adult rats. We showed that fourth intracerebroventricular delivery of MC3/4R agonist and antagonist increased and decreased the BDNF protein content within the DVC, respectively. Second, we showed that the orexigenic effect of a selective MC4R antagonist delivered fourth-icv can be blocked by a coadministration of BDNF. We also tested the causal role of BDNF/TrkB signaling in the anorexigenic effect of melanocortinergic signaling by using a recently developed analog-sensitive kinase allele murine model (TrkBF616A mice) and showed that the pharmacological blockade of TrkB abolished the anorexigenic effect of a selective MC4R agonist and of cholecystokinin. Our results provide strong evidence for a role of BDNF as a downstream effector of melanocortinergic signaling pathway within the DVC.
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BDNF may be a downstream effector of MC4R.
“In rats, injection of anti-brain-derived neurotrophic factor (BDNF) antibody into the CNS blunted the anorexic effect of MC4R activation, suggesting that BDNF may be a downstream effector of MC4R211.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [211]
In rats, injection of anti-brain-derived neurotrophic factor antibody into the central nervous system blunted the anorexic effect of MC4R activation.
“In rats, injection of anti-brain-derived neurotrophic factor (BDNF) antibody into the CNS blunted the anorexic effect of MC4R activation, suggesting that BDNF may be a downstream effector of MC4R211.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [211]
The melanocortin system also plays an important role in regulating sympathetic nervous system activity and blood pressure besides its effects on food intake and body weight regulation.
“Besides its effects on food intake and body weight regulation, the melanocortin system also plays an important role in regulating SNS activity and BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [8]
Melanocortins play an important role in regulating blood pressure and sympathetic nervous system activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals.
“Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [8]
Pharmacological activation or inhibition of MC4R, respectively, increased and reduced BDNF protein content in the dorsal motor nucleus of the vagus of adult rats.
“Studies by Bariohay et al showed that pharmacological activation or inhibition of MC4R, respectively, increased and reduced BDNF protein content in the DMV of adult rats [8].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [8]
The orexigenic effect of a selective MC4R antagonist injected into the fourth ventricle was completely blocked by co-administration of BDNF.
“In addition, the orexigenic effect of a selective MC4R antagonist injected into the 4th ventricle was completely blocked by co-administration of BDNF [8].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [8]
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- Authors
- Bariohay, B., Roux, J., Tardivel, C., Trouslard, J., Jean, A., & Lebrun, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Centre de Recherche de Neurobiologie et Neurophysiologie de Marseille, Département de Physiologie Neurovégétative, Université Paul Cézanne, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6231, Institut National de la Recherche Agronomique Unité sous contrat 2027, Faculté des Sciences et Techniques de Saint-Jérôme, F-13397 Marseille Cedex 20, France
- Corresponding author
- Lebrun, Bruno
- ORCID
- Lebrun, Bruno
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-01-29
- Volume
- 150
- Issue
- 6
- Pages
- 2646-2653
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2082057007
- Cited by
- 95
- References
- 36
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 8 · 2016: 5 · 2015: 12 · 2014: 8 · 2013: 16 · 2012: 11
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Princeton University
- Centre National de la Recherche Scientifique
- Institut National de la Recherche Agronomique
- Région Normandie
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- brain-derived neurotrophic factor, TrkB receptor, melanocortin system, dorsal vagal complex, food intake regulation, melanocortin-4 receptor, melanocortin 3 receptor, cholecystokinin, orexigenic effect, satiety signals
- MeSH terms
- alpha-MSH, Animals, Appetite Regulation, Brain Stem, Cholecystokinin, Injections, Intraventricular, Male, Melanocyte-Stimulating Hormones, Peptides, Cyclic, Signal Transduction, Rats, Wistar, Mice, Knockout, Brain-Derived Neurotrophic Factor, Receptor, trkB, Models, Animal, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Mice, Rats, Melanocortins
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