LRb signals act within a distributed network of leptin‐responsive neurones to mediate leptin action
Abstract
The adipose tissue‐derived hormone, leptin, acts via its receptor (LRb) in the brain to regulate energy balance and neuroendocrine function. In order to understand leptin action we have explored the physiological function of LRb signalling pathways, defining important roles for signal transducer and activator of transcription‐3 (STAT3) in positive signalling and for LRbTyr 985‐mediated feedback inhibition in leptin signal attenuation. As the cells on which leptin acts are not homogeneous, but rather represent a broadly distributed network of neurones with divergent projections and functions, it is also crucial to consider how each of these populations responds to LRb signals to contribute to leptin action. While well‐known LRb‐expressing neurones within the arcuate nucleus of the hypothalamus mediate crucial effects on satiety and energy expenditure, other populations of LRb‐expressing neurones in the ventral tegmental area and elsewhere likely control the mesolimbic dopamine system. Additional populations of LRb‐expressing neurones likely contribute to other aspects of neuroendocrine regulation. It will be important to define the molecular mechanisms by which leptin acts to regulate neurophysiology in each of these LRb‐expressing neural populations in order to understand the totality of leptin action.
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Leptin receptors are located in hypothalamic areas beyond the arcuate nucleus, including the ventromedial, dorsomedial, premammillary, lateral, and perifornical areas, where they likely contribute to leptin's effects on food intake and energy expenditure.
“But clearly, leptin receptors are located in other hypothalamic areas such as the ventromedial, dorsomedial, and premammillary nuclei, as well as the lateral and perifornical areas where they likely contribute to leptin's effects on food intake and energy expenditure”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [102]
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Ellacott, K. L. J., & Cone, R. D. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1861 · Cited by 134 · see citing works
Characterization of Leptin-Responsive Neurons in the Caudal Brainstem
Ellacott, K. L. J., Halatchev, I. G., & Cone, R. D. (2006) · Endocrinology · doi:10.1210/en.2005-0877 · Cited by 133 · see citing works
Couturier, C., & Jockers, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302002200 · Cited by 132 · see citing works
Pleiotropy of leptin receptor signalling is defined by distinct roles of the intracellular tyrosines
Hekerman, P., Zeidler, J., Bamberg‐Lemper, S., Knobelspies, H., Lavens, D., Tavernier, J., Joost, H., & Becker, W. (2004) · The FEBS Journal · doi:10.1111/j.1432-1033.2004.04391.x · Cited by 129 · see citing works
Tyrosine Phosphorylation of Jak2 in the JH2 Domain Inhibits Cytokine Signaling
Feener, E. P., Rosario, F., Dunn, S. L., Stancheva, Z. S., & Myers, M. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.11.4968-4978.2004 · Cited by 113 · see citing works
Self-citationTyrosine 813 Is a Site of JAK2 Autophosphorylation Critical for Activation of JAK2 by SH2-Bβ
Kurzer, J. H., Argetsinger, L. S., Zhou, Y.-J., Kouadio, J.-L. K., O’Shea, J. J., & Carter‐Su, C. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.10.4557-4570.2004 · Cited by 107 · see citing works
Funakoshi-Tago, M., Pelletier, S., Matsuda, T., Parganas, E., & Ihle, J. (2006) · EMBO Journal · doi:10.1038/sj.emboj.7601365 · Cited by 89 · see citing works
Münzberg, H., Jobst, E. E., Bates, S. H., Jones, J. C., Villanueva, E. C., Leshan, R. L., Björnholm, M., Elmquist, J. K., Sleeman, M. W., Cowley, M. A., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3168-06.2007 · Cited by 86 · see citing works
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Bodary, P. F., Shen, Y., Öhman, M. K., Bahrou, K. L., Vargas, F. B., Cudney, S. S., Wickenheiser, K. J., Myers, M. G., & Eitzman, D. T. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000252068.89775.ee · Cited by 67 · see citing works
Self-citationCharacterization and Binding Specificity of the Monomeric STAT3-SH2 Domain*
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Phosphorylation of Jak2 on Ser 523 InhibitsJak2-Dependent Leptin ReceptorSignaling
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Self-citationSmith, M. A., Hisadome, K., Al‐Qassab, H., Heffron, H., Withers, D. J., & Ashford, M. L. J. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.119479 · Cited by 60 · see citing works
盛, 裕. (2006) · Medical Entomology and Zoology · Cited by 58 · see citing works
Determination of the transphosphorylation sites of Jak2 kinase
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Food restriction and leptin impact brain reward circuitry in lean and obese Zucker rats
Fulton, S. E., Richard, D., Woodside, B. C., & Shizgal, P. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.05.021 · Cited by 39 · see citing works
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Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
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Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · see citing works
Evidence for defective mesolimbic dopamine exocytosis in obesity‐prone rats
Geiger, B. M., Behr, G. G., Frank, L. E., Caldera-Siu, A. D., Beinfeld, M. C., Kokkotou, E. G., & Pothos, E. N. (2008) · The FASEB Journal · doi:10.1096/fj.08-110759 · Cited by 194 · see citing works
- Authors
- Leinninger, G. M., & Myers, M. G.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Myers, M. G.
- Venue
- Acta Physiologica
- Publisher
- Wiley
- Published
- 2007-10-29
- Volume
- 192
- Issue
- 1
- Pages
- 49-59
- ISSN
- 1748-1708 (ISSN-L)
- 1748-1716
- OpenAlex
- W2156661755
- Cited by
- 56
- References
- 108
- Citations by year
- 2025: 2 · 2024: 1 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 5
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Physiologica (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (acceptedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, leptin receptor, STAT3 signaling, hypothalamic arcuate nucleus, ventral tegmental area, mesolimbic dopamine system, energy balance, neuroendocrine regulation, satiety, energy expenditure
- MeSH terms
- Animals, Cytoskeletal Proteins, Female, Humans, Mutation, Nerve Tissue Proteins, Neural Pathways, Neurons, Signal Transduction, Mice, Knockout, Leptin, STAT3 Transcription Factor, Mice, Receptors, Leptin
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.
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