The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity
Open accessAbstract
The neuronal circuits involved in the regulation of feeding behavior and energy expenditure are soft-wired, reflecting the relative activity of the postsynaptic neuronal system, including the anorexigenic proopiomelanocortin (POMC)-expressing cells of the arcuate nucleus. We analyzed the synaptic input organization of the melanocortin system in lean rats that were vulnerable (DIO) or resistant (DR) to diet-induced obesity. We found a distinct difference in the quantitative and qualitative synaptology of POMC cells between DIO and DR animals, with a significantly greater number of inhibitory inputs in the POMC neurons in DIO rats compared with DR rats. When exposed to a high-fat diet (HFD), the POMC cells of DIO animals lost synapses, whereas those of DR rats recruited connections. In both DIO rats and mice, the HFD-triggered loss of synapses on POMC neurons was associated with increased glial ensheathment of the POMC perikarya. The altered synaptic organization of HFD-fed animals promoted increased POMC tone and a decrease in the stimulatory connections onto the neighboring neuropeptide Y (NPY) cells. Exposure to HFD was associated with reactive gliosis, and this affected the structure of the blood-brain barrier such that the POMC and NPY cell bodies and dendrites became less accessible to blood vessels. Taken together, these data suggest that consumption of an HFD has a major impact on the cytoarchitecture of the arcuate nucleus in vulnerable subjects, with changes that might be irreversible due to reactive gliosis.
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Cites
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Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
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Self-citationClinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
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Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
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“Consistent with this conclusion from our current observations is the fact that the synaptic input organization of POMC neurons on an HFD with elevated leptin levels shows a similar trend of changes as those that we described previously for highly sensitive ob/ob mice in response to leptin administration (12).”
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“Although it is established that changes in hypothalamic synaptic plasticity of satiety-promoting melanocortin neurons can be triggered by afferent (energy balance–regulating) hormones such as leptin, estradiol, and ghrelin (12, 16), it is almost certain that the individual variability of wiring and overall flexibility…”
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Obesity is associated with hypothalamic injury in rodents and humans.
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Self-citationHypothalamic inflammation in obesity and metabolic disease
Jais, A., & Brüning, J. C. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88878 · Cited by 474
Sixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367
Impact of Metabolic Syndrome on Neuroinflammation and the Blood–Brain Barrier
Van Dyken, P., & Lacoste, B. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00930 · Cited by 359
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim, J. G., Suyama, S., Koch, M., Jin, S., Argente-Arizon, P., Argente, J., Liu, Z.-W., Zimmer, M. R., Jeong, J. K., Szigeti-Buck, K., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3725 · Cited by 336
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Metadata
- Authors
- Horvath, T. L., Sarman, B., García-Cáceres, C., Enriori, P. J., Sotonyi, P., Shanabrough, M., Borok, E., Argente, J., Chowen, J. A., Perez-Tilve, D., Pfluger, P. T., Brönneke, H. S., Levin, B. E., Diano, S., Cowley, M. A., & Tschöp, M. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-08-02
- Volume
- 107
- Issue
- 33
- Pages
- 14875-14880
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2077335475
- Cited by
- 444
- References
- 37
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Horvath, T. L., Sarman, B., García-Cáceres, C., Enriori, P. J., Sotonyi, P., Shanabrough, M., Borok, E., Argente, J., Chowen, J. A., Perez-Tilve, D., Pfluger, P. T., Brönneke, H. S., Levin, B. E., Diano, S., Cowley, M. A., & Tschöp, M. H. (2010). Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1004282107
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