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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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“First Published Online July 26, 2013 Abbreviations: AgRP, agouti-related protein; ANCOVA, analysis of covariance; ARC, arcuate nucleus; BDNF, brain-derived neurotrophic factor; CART, cocaine- and amphetamine-regulated transcript; CNS, central nervous system; CONV-R, conventionally raised; ER, endoplasmic reticulum; fw…”
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BackgroundA fresh look at NASH pathogenesis. Part 1: The metabolic movers
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“Evidence suggests that these POMC neurons express leptin receptors and that central MC signaling contributes to the effects of the adipocyte hormone leptin (Cheung et al., 1997; Mountjoy and Wong, 1997; Seeley et al., 1997).”
BackgroundBody weight is regulated by the brain: a link between feeding and emotion
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“For example, most of POMC-expressing Arc neurons coexpress Ob-Rb mRNA”
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“The ObRb is mainly expressed by two distinct neuronal populations in the hypothalamic arcuate nucleus (ARC): the anorexigenic (appetite-depressing) POMC (pro-opiomelanocortin) neurons and the orexigenic (appetite-promoting) NPY/AgRP (neuropeptide Y/agouti-related peptide) neurons (80, 81) (Figure 2).”
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“Whether the former effect is predominantly permissive remains to be seen, and further investigation of the insulin-leptin-ghrelin-POMC-NPY interplay with regard to reproduction is likely to provide some answers in future.”
InfluentialMetabolic impact of sex hormones on obesity
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“Leprb is expressed by two populations of ARC neurons, those expressing proopiomelanocortin (POMC) (Cheung et al., 1997; Thornton et al., 1997) and those expressing NPY and agouti-related peptide (NPY/AgRP neurons) (Baskin et al.”
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“In the ARC, approximately 30% of the POMC-expressing neurons carry the Ob-Rb receptor (Cheung et al. 1997).”
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“Anorexigenic proopiomelanocortin (POMC) neurons in the arcuate nucleus also contain LepR mRNA (Cheung et al. 1997) and leptin increases the level of POMC mRNA (Schwartz et al.”
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BackgroundBrain Pathways Controlling Food Intake and Body Weight
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“Evidence that these POMC neurons are involved in energy homeostasis stems from observations that both chronic caloric restriction and acute energy deprivation reduce POMC gene expression in the arcuate nucleus (11, 12), and that pharmacological blockade of CNS melanocortin receptors causes hyperphagia and weight gain…”
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“Collectively, these findings suggest that ESR1 functions in POMC neurons to influence energy homeostasis and may provide a mechanism for the anorexigenic effects of E2.”
InfluentialActivation of Stat3 Signaling in AgRP Neurons Promotes Locomotor Activity
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Neural melanocortin receptors in obesity and related metabolic disorders
Girardet, C., & Butler, A. A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.05.004 · Cited by 128
Huo, L., Grill, H. J., & Bjørbæk, C. (2006) · Diabetes · doi:10.2337/diabetes.55.03.06.db05-1143 · Cited by 127
“One group of leptin-responsive neurons are the proopiomelanocortin (POMC) cells located in the arcuate nucleus (ARC) of hypothalamus (4,5).”
GENETIC MODELS OF OBESITY AND ENERGY BALANCE IN THE MOUSE
Robinson, S. W., Dinulescu, D. M., & Cone, R. D. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.687 · Cited by 122
The Role of PVH Circuits in Leptin Action and Energy Balance
Sutton, A. K., Myers, M. G., & Olson, D. P. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105347 · Cited by 126
Leptin: a modulator of alcohol craving?
Kiefer, F., Jahn, H., Jaschinski, M., et al. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01081-2 · Cited by 122
Watanobe, H. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.023895 · Cited by 125
“This attempt was made based on previous reports that the hypothalamo–pituitary–gonadal axis showed differential responses to exogenous leptin in fed vs. foodrestricted animals (Cheung et al. 1997b; Henry et al. 1999, 2001; Nagatani et al. 2001).”
BackgroundResultElectrophysiological Actions of Peripheral Hormones on Melanocortin Neurons
Cowley, M. A., Cone, R. D., Enriori, P. J., Louiselle, I., Williams, S., & Evans, A. E. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03178.x · Cited by 122
Caron, A., Lemko, H. M. D., Castorena, C. M., Fujikawa, T., Lee, S., Lord, C. C., Ahmed, N. I., Lee, C. E., Holland, W. L., Liu, C., et al. (2018) · eLife · doi:10.7554/elife.33710 · Cited by 122
Jacobson, P., Ukkola, O. H., Rankinen, T., Snyder, E. E., Leon, A. S., Rao, D. C., Skinner, J. S., Wilmore, J. H., Lönn, L., Cowan, G. S. M., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020568 · Cited by 119
Reddy, A. B., Cronin, A. S., Ford, H., & Ebling, F. J. P. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00746.x · Cited by 120
“A proportion of both NPY- and POMC-containing neurons in the mediobasal hypothalamus have been shown to colocalize the long form of the leptin receptor in rats (Cheung et al., 1997; Hakansson et al., 1998) and mice (NPY only: Mercer et al., 1996).”
BackgroundGhrelin and the Regulation of Food Intake and Energy Balance
Hosoda, H. (2002) · Molecular Interventions · doi:10.1124/mi.2.8.494 · Cited by 116
“Most NPY–AGRP–producing, or POMC–CART–producing neurons also express leptin receptors, and both types of neurons are regulated by leptin, albeit in an opposing manner (87, 88).”
BackgroundMode of action of OB protein (leptin) on feeding
Flynn, M. C., Scott, T. R., Pritchard, T. C., & Plata‐Saláman, C. R. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.1.r174 · Cited by 119
“OB protein also modulates proopiomelanocortin neurons (4), hypothalamic melanocortin receptor subtypes action (8), and the corticotropin-releasing factor-ACTHglucocorticoid pathway (23).”
BackgroundMastorakos, G. P., & Zapanti, E. D. (2004) · Nutritional Neuroscience · doi:10.1080/10284150400020516 · Cited by 119
“Proopiomelanocortin producing neurons express leptin receptor (Cheung et al., 1997).”
The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors
Diniz, G. B., & Bittencourt, J. C. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00032 · Cited by 118
“…et al., 2003), glucose (Leloup et al., 1994; Muroya et al., 1999; Parton et al., 2007), and leptin (Mercer et al., 1996; Schwartz et al., 1996; Cheung et al., 1997), all of them capable of conveying the short- and long-term energetic state of the organism from the CSF to the Arc through the…”
BackgroundEnergy regulatory signals and food reward
Figlewicz, D. P., & Sipols, A. J. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.03.002 · Cited by 116
“POMC and AgRP are selectively expressed in neurons of the ARC colocalized with receptors for insulin and leptin, and they are endogenous circuitry capable of regulating food intake (Cheung et al., 1997; Mizuno et al., 1999; Mountjoy and Wong, 1997).”
BackgroundPRL-Releasing Peptide Interacts with Leptin to Reduce Food Intake and Body Weight
Ellacott, K. L. J., Lawrence, C. B., Rothwell, N. J., & Luckman, S. M. (2002) · Endocrinology · doi:10.1210/endo.143.2.8608 · Cited by 116
“This phenomenon has been reported for a number of other anorexigenic peptides including cocaine- and amphetamineregulated transcript (32), POMC (47), and CRH (48).”
Anti-obesity drugs: a critical review of current therapies and future opportunities
Clapham, J. C. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(00)00105-4 · Cited by 111
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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