Synaptic Plasticity in Energy Balance Regulation
Open accessAbstract
Leptin regulates energy balance, in part, by modulating the activity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus. Leptin‐deficient (ob/ob) mice differ from wild‐type mice in the number of excitatory and inhibitory post‐synaptic densities and currents onto NPY and POMC neurons. When leptin was delivered to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake. Synaptic currents were also shifted toward wild‐type values in leptin‐replaced ob/ob mice. These data suggest that leptin‐mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's behavioral effects. In an effort to determine whether the observed synaptic plasticity is leptin specific, we analyzed the effects of an orexigenic hormone, ghrelin, and anorexigenic hormone, estradiol. Ghrelin rearranged synapses in wild type animals to support suppressed POMC tone, whereas the estradiol triggered a robust increase in the number of excitatory, glutamate inputs of POMC neurons. The rearrangement of synapses by estradiol was leptin independent, because it was also evident in leptin‐ (ob/ob) and leptin receptor–deficient (db/db) mice and was paralleled with decreased food intake and increased energy expenditure in these mutant, obese animals. Such plasticity was also observed in other hypothalamic regions and extrahypothalamic sites. These observations raise the notion that synaptic plasticity is a major way through which peripheral metabolic hormones influence brain functions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Regulation of spontaneous firing of AgRP neurons can be achieved by synaptic and intrinsic mechanisms.
“Regulation of spontaneous firing of AgRP neurons can be achieved by synaptic and intrinsic mechanisms [54, 58–61].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [60]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults
Calle, E. E., Rodriguez, C., Walker-Thurmond, K., & Thun, M. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021423 · Cited by 7,696 · see citing works
Prevalence and trends in obesity among US adults, 1999–2000
Flegal, K. M. (2002) · JAMA · doi:10.1001/jama.288.14.1723 · Cited by 6,190 · see citing works
Weight-Reducing Effects of the Plasma Protein Encoded by the <i>obese</i> Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451 · see citing works
Effects of the <i>obese</i> Gene Product on Body Weight Regulation in <i>ob</i> / <i>ob</i> Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017 · see citing works
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243 · see citing works
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,902 · see citing works
Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight
Kalra, S. P., Dube, M. G., Pu, S., Xu, B., Horváth, T. L., & Kalra, P. S. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.1.0357 · Cited by 1,556 · see citing works
Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight
Kalra, S. P. (1999) · Endocrine Reviews · doi:10.1210/er.20.1.68 · Cited by 1,554 · see citing works
The role of neuropeptide Y in the antiobesity action of the obese gene product
Stephens, T. W., Basinski, M., Bristow, P. K., Bue-Valleskey, J. M., Burgett, S. G., Craft, L., Hale, J., Hoffmann, J., Hsiung, H. M., Kriauciunas, A., et al. (1995) · Nature · doi:10.1038/377530a0 · Cited by 1,498 · see citing works
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164 · see citing works
Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice.
Vaisse, C., Halaas, J. L., Horvath, C. M., Darnell, J. E., Stoffel, M., & Friedman, J. M. (1996) · Nature Genetics · doi:10.1038/ng0996-95 · Cited by 1,086 · see citing works
STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Bates, S. H., Stearns, W. H., Dundon, T. A., Schubert, M., Tso, A. W. K., Wang, Y., Banks, A. S., Lavery, H. J., Haq, A. K., Maratos-Flier, E., et al. (2003) · Nature · doi:10.1038/nature01388 · Cited by 1,010 · see citing works
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto, S., Roseberry, A. G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J. M., & Horvath, T. L. (2004) · Science · doi:10.1126/science.1089459 · Cited by 987 · see citing works
Self-citationLeptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G. (1997) · Diabetes · doi:10.2337/diab.46.12.2119 · Cited by 879 · see citing works
Ghrelin controls hippocampal spine synapse density and memory performance
Diano, S., Farr, S. A., Benoit, S. C., McNay, E. C., da Silva, I., Horvath, B., Gaskin, F. S., Nonaka, N., Jaeger, L. B., Banks, W. A., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1656 · Cited by 828 · see citing works
Key enzyme in leptin-induced anorexia
Niswender, K. D., Morton, G. J., Stearns, W. H., Rhodes, C. J., Myers, M. G., & Schwartz, M. W. (2001) · Nature · doi:10.1038/35101657 · Cited by 585 · see citing works
Mizuno, T. M., Kleopoulos, S. P., Bergen, H., Roberts, J. L., Priest, C. A., & Mobbs, C. V. (1998) · Diabetes · doi:10.2337/diab.47.2.294 · Cited by 521 · see citing works
Unraveling the central nervous system pathways underlying responses to leptin
Elmquist, J. K., Maratos-Flier, E., Saper, C. B., & Flier, J. S. (1998) · Nature Neuroscience · doi:10.1038/2164 · Cited by 520 · see citing works
Eckel, R. H. (1997) · Circulation · doi:10.1161/01.cir.96.9.3248 · Cited by 512 · see citing works
Horváth, T. L., Diano, S., & van den Pol, A. N. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-03-01072.1999 · Cited by 504 · see citing works
Zarjevski, N., Cusin, I., Vettor, R., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404618 · Cited by 476 · see citing works
Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus
Niswender, K. D., Morrison, C. D., Clegg, D. J., Olson, R., Baskin, D. G., Myers, M. G., Seeley, R. J., & Schwartz, M. W. (2003) · Diabetes · doi:10.2337/diabetes.52.2.227 · Cited by 476 · see citing works
Mercer, J. G., Hoggard, N., Williams, L. M., Lawrence, C. B., Hannah, L. T., Morgan, P. J., & Trayhurn, P. (1996) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1996.05161.x · Cited by 460 · see citing works
Long‐Term Safety and Efficacy of Circumferential Ablation with Pulmonary Vein Isolation
Cheema, A., Dong, J., Dalal, D., Vasamreddy, C. R., Marine, J. E., Henrikson, C. A., SPRAGG, D. D., Cheng, A., Nazarian, S., Sinha, S. K., et al. (2006) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2006.00569.x · Cited by 452 · see citing works
Genetic approaches to studying energy balance: perception and integration
Barsh, G. S., & Schwartz, M. W. (2002) · Nature Reviews Genetics · doi:10.1038/nrg862 · Cited by 417 · see citing works
The Neuroanatomical Axis for Control of Energy Balance
Grill, H. J., & Kaplan, J. M. (2002) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2001.0224 · Cited by 395 · see citing works
Gao, Q., Wolfgang, M. J., Neschen, S., Morino, K., Horvath, T. L., Shulman, G. I., & Fu, X.-Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0303992101 · Cited by 385 · see citing works
Self-citationBaskin, D. G., Breininger, J. F., & Schwartz, M. W. (1999) · Diabetes · doi:10.2337/diabetes.48.4.828 · Cited by 351 · see citing works
The role of gastrointestinal vagal afferents in the control of food intake: current prospects
Schwartz, G. J. (2000) · Nutrition · doi:10.1016/s0899-9007(00)00464-0 · Cited by 294 · see citing works
Theodosis, D. T., Rougon, G. N., & Poulain, D. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5494 · Cited by 238 · see citing works
Input organization and plasticity of hypocretin neurons
Horváth, T. L., & Gao, X. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.03.003 · Cited by 198 · see citing works
Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain
Lin, S., Storlien, L. H., & Huang, X. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02580-4 · Cited by 194 · see citing works
Diano, S., Matthews, R. T., Patrylo, P. R., Yang, L., Beal, M. F., Barnstable, C. J., & Horváth, T. L. (2003) · Endocrinology · doi:10.1210/en.2003-0667 · Cited by 186 · see citing works
Synaptic remodelling in arcuate nucleus after injection of estradiol valerate in adult female rats
García‐Segura, L. M., Baetens, D., & Naftolin, F. N. (1986) · Brain Research · doi:10.1016/0006-8993(86)91287-4 · Cited by 142 · see citing works
Stern, J. E., & Armstrong, W. E. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-03-00841.1998 · Cited by 130 · see citing works
The floating blueprint of hypothalamic feeding circuits
Horváth, T. L., & Diano, S. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1479 · Cited by 102 · see citing works
Xiong, J.-J., Karsch, F. J., & Lehman, M. N. (1997) · Endocrinology · doi:10.1210/endo.138.3.5000 · Cited by 86 · see citing works
Miyata, S., Nakashima, T., & Kiyohara, T. (1994) · Brain Research Bulletin · doi:10.1016/0361-9230(94)90057-4 · Cited by 67 · see citing works
Zsarnovszky, A., Horváth, T. L., García‐Segura, L. M., Horváth, B., & Naftolin, F. N. (2001) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2001.00602.x · Cited by 39 · see citing works
Xiong, J.-J. (1997) · Endocrinology · doi:10.1210/en.138.3.1240 · Cited by 36 · see citing works
Estradiol affects axo-somatic contacts of neuroendocrine cells in the arcuate nucleus of adult rats
Párducz, Á., Zsarnovszky, A., Naftolin, F. N., & Horváth, T. L. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00967-3 · Cited by 33 · see citing works
Zsarnovszky, A., Horváth, T. L., García‐Segura, L. M., Horváth, B., & Naftolin, F. N. (2001) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2001.00602.x · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Estrogen deficiency and the origin of obesity during menopause
Lizcano, F., & Guzmán, G. (2014) · BioMed Research International · doi:10.1155/2014/757461 · Cited by 586 · see citing works
Loss of GABAergic Signaling by AgRP Neurons to the Parabrachial Nucleus Leads to Starvation
Wu, Q., Boyle, M. P., & Palmiter, R. D. (2009) · Cell · doi:10.1016/j.cell.2009.04.022 · Cited by 465 · see citing works
Hypothalamic inflammation in obesity and metabolic disease
Jais, A., & Brüning, J. C. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88878 · Cited by 474 · see citing works
Estrogen Receptors and the Metabolic Network
Barros, R. P. A., & Gustafsson, J.-Å. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.005 · Cited by 458 · see citing works
Central and Peripheral Regulation of Food Intake and Physical Activity: Pathways and Genes
Lenard, N. R., & Berthoud, H. (2008) · Obesity · doi:10.1038/oby.2008.511 · Cited by 338 · see citing works
Synaptic plasticity in neuronal circuits regulating energy balance
Zeltser, L. M., Seeley, R. J., & Tschöp, M. H. (2012) · Nature Neuroscience · doi:10.1038/nn.3219 · Cited by 147 · see citing works
Wiedmer, P., Nogueiras, R., Broglio, F., D'Alessio, D., & Tschöp, M. H. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0625 · Cited by 111 · see citing works
Fang, X., Jiang, S., Wang, J., Bai, Y., Kim, C. S., Blake, D., Weintraub, N. L., Lei, Y., & Lu, X.-Y. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-01004-x · Cited by 95 · see citing works
Oestrogen Modulates Hypothalamic Control of Energy Homeostasis Through Multiple Mechanisms
Roepke, T. A. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01814.x · Cited by 90 · see citing works
- Authors
- Horvath, T. L.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2006-08
- Volume
- 14
- Issue
- S8
- Pages
- 228S-233S
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- OpenAlex
- W2084769437
- Cited by
- 104
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 9 · 2012: 8
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- 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 › Neuroscience and Neuropharmacology Research
- Keywords
- synaptic plasticity, energy balance, leptin, ob/ob mice, POMC neurons, NPY neurons, arcuate nucleus, hypothalamus, ghrelin, estradiol, glutamatergic synapses, dietary intake, energy expenditure, leptin receptor, db/db mice, metabolic hormones
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Energy Metabolism, Estradiol, Mice, Obese, Neuronal Plasticity, Neuropeptide Y, Pro-Opiomelanocortin, Peptide Hormones, Mice, Ghrelin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review