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Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus
Abstract
Leptin is a protein product of the obese (ob) gene, which is secreted by adipocytes and functions as a satiety factor to regulate food intake. The expression of the leptin receptor in several hypothalamic nuclei suggests that multiple neuronal subtypes are targets for leptin's action. Products of the proopiomelanocortin (POMC) gene are known to affect feeding behavior, and POMC neurons share a similar distribution with leptin receptor mRNA in the arcuate nucleus. We used double label in situ hybridization and computerized image analysis to test the hypothesis that POMC neurons coexpress the leptin receptor. Quantitative analysis confirmed that POMC neurons in the hypothalamus express leptin receptor mRNA. Based on this observation, we infer that POMC neurons and the products of the POMC gene may be part of the signaling pathway mediating leptin's action on feeding and perhaps other physiological functions.
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“POMC neurons are stimulated by leptin (33, 162)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [33]
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Peng, C., Mukhopadhyay, A., Jarrett, J. C., Yoshikawa, K., & Kessler, J. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2484-12.2012 · Cited by 34
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Boyle, C. N., & Lutz, T. A. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.02.015 · Cited by 31
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“Ob–Rb, the long form of leptin receptor, has been colocalized with NPY/AgRP and POMC/CART in the ARC neurons and with MCH and orexins in the LHA neurons (Mercer et al., 1997; Cheung et al., 1997; Baskin et al., 1999; Cowley et al., 2001).”
Physiological Mechanisms Integrating Metabolism and Reproduction
Krasnow, S. M., & Steiner, R. D. (2006) · Elsevier eBooks · doi:10.1016/b978-012515400-0/50052-x · Cited by 33
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“Leptin has been shown to increase the firing rate of POMC neurons [14], and both leptin and insulin stimulate POMC gene expression [56–58].”
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Physiological endocrine control of energy homeostasis and postprandial blood glucose levels.
Gagliardino, J. J. (2005) · PubMed · Cited by 21
Shih, C.-D., Au, L., & Chen, J. Y. H. (2003) · Journal of Biomedical Science · doi:10.1007/bf02256428 · Cited by 22
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“Furthermore, AGRP[83–132], prepared synthetically and folded in vitro, was demonstrated to block I-NDP-MSH binding to the hMC3-R (3.”
BackgroundSánchez, J., Cladera, M. M., Llopis, M., Palou, A., & Picó, C. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.04.051 · Cited by 19
Li, J.-Y., Chai, B.-X., Zhang, W., Wang, H., & Mulholland, M. W. (2009) · Endocrinology · doi:10.1210/en.2009-0560 · Cited by 19
Piattini, F., Foll, C. L., Kisielow, J., Rosenwald, E., Nielsen, P., Lutz, T. A., Schneider, C., & Köpf, M. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.04.010 · Cited by 21
“Under homeostatic conditions, leptin stimulates catabolic POMC neurons and POMC expression [21,23] but inhibits AgRP neurons and AgRP expression [24,25].”
Network dynamics of hypothalamic feeding neurons
Sweeney, P., Chen, C., Rajapakse, I., & Cone, R. D. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2011140118 · Cited by 19
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“As hypothalamic POMC neurons express leptin receptor mRNA [33] and leptin has been demonstrated to stimulate POMC gene expression [33, 34], it is reasonable to hypothesize that the melatonin-induced decrease in forebrain opiomelanocortin gene expression in the current study may have been in part mediated by melatonin-…”
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Attenuated pain response of obese mice (B6.Cg-lep) is affected by aging and leptin but not sex
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“Leptin plays a role in many processes, including weight regulation [4], POMC production [33], obesity [34], diabetes [35,36], glucocorticoids [37], endogenous opioids [38] and endocannabinoids [12].”
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“Leptin activates POMC neurons and suppresses agouti-related protein (AGRP) in the arcuate nucleus (ARC), resulting in a rise in Pomc expression and a reduction in Agrp mRNA [14–18].”
Background
Metadata
- Authors
- Cheung, C. C., Clifton, D. K., & Steiner, R. A.
- Affiliations
- University of Washington (US)
- Corresponding author
- Steiner, Robert A.
- ORCID
- Steiner, Robert A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1997-10
- Volume
- 138
- Issue
- 10
- Pages
- 4489-4492
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2129221666
- Cited by
- 769
- References
- 0
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 14 · 2017: 18 · 2016: 15 · 2015: 24 · 2014: 20 · 2013: 30 · 2012: 34
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5t32gm007108-40)
- National Institute of General Medical Sciences (5 T32-GM07108)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 27142, R01HD027142)
- 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 › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, proopiomelanocortin, POMC neurons, leptin receptor, hypothalamus, arcuate nucleus, feeding behavior, satiety, food intake regulation, obese gene
- MeSH terms
- Animals, Carrier Proteins, Eating, Female, Gene Expression Regulation, Hypothalamus, Image Processing, Computer-Assisted, Neurons, Pro-Opiomelanocortin, Proteins, Receptors, Cell Surface, RNA, Messenger, Signal Transduction, Rats, Sprague-Dawley, In Situ Hybridization, Leptin, Rats, Receptors, Leptin
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