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Regulation of Hypothalamic Proopiomelanocortin mRNA by Leptin in ob/ob Mice
Abstract
The hormone leptin acts on the brain to regulate feeding, metabolism, and reproduction; however, its cellular targets and molecular mechanisms of action remain to be fully elucidated. The melanocortins, which are derived from the precursor proopiomelanocortin (POMC), are also implicated in the physiological regulation of body weight. POMC-containing neurons express the leptin receptor, and thus it is conceivable that the POMC gene itself may be part of the signaling pathway involved in leptin's action on the brain. Using in situ hybridization and computerized image analysis, we tested the hypothesis that the POMC gene is a target for regulation by leptin by comparing cellular levels of POMC mRNA in the hypothalamus among groups of leptin-deficient (ob/ob) mice, leptin-treated ob/ob mice, and wild-type controls. POMC mRNA levels were significantly reduced throughout the arcuate nucleus in vehicle-treated ob/ob mice relative to wild-type controls, whereas POMC mRNA levels in leptin-treated ob/ob mice were indistinguishable from wild-type controls. These observations suggest that one or more products of POMC serve as an integrative link between leptin and the central mechanisms governing body weight regulation and reproduction.
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“HA-ObRb/Pomc-Cre/Leprdb/db mice had modestly increased hypothalamic POMC mRNA (Figure 6A) consistent with a role of leptin signaling to stimulate Pomc gene expression (Munzberg et al., 2003; Thornton et al., 1997).”
From Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons (2009) · cites this paper as Thornton et al., 1997
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“Furthermore, aMSH, a POMC peptide product, may contribute to leptin’s in_uence on the initiation of puberty, as aMSH has been reported to stimulate sexual maturation [12,82–85].”
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BackgroundRole for Leptin and Leptin Receptors in Stem Cells During Health and Diseases
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“The nature of the mechanisms that underlie these differential effects on body weight and adiposity in LepTg mice with and without 5HT2c receptors was addressed by measuring the relative expression levels of the orexigenic neuropeptides NPY, AgRP and anorexigenic neuropeptides POMC and CART, which are respectively down…”
BackgroundBMP Receptor 1A Regulates Development of Hypothalamic Circuits Critical for Feeding Behavior
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
“Subpopulations of ARH neurons upregulate POMC or downregulate NPY/AgRP expression in response to leptin signaling to modulate energy balance (Stephens et al., 1995; Erickson et al., 1996; Thornton et al., 1997).”
BackgroundAgouti-related protein: More than a melanocortin-4 receptor antagonist?
Pritchard, L. E., & White, A. E. (2005) · Peptides · doi:10.1016/j.peptides.2004.11.036 · Cited by 30
Ahi, E. P., Brunel, M., Tsakoumis, E., & Schmitz, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-56779-z · Cited by 29
Vugt, D. A. V., Lujan, M. E., Froats, M., et al. (2006) · Neuroendocrinology · doi:10.1159/000097494 · Cited by 29
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
Self-citationRenz, M. E., Tomlinson, E., Hultgren, B., Levin, N., Gu, Q., Shimkets, R. A., Lewin, D. A., & Stewart, T. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10429 · Cited by 29
Bone loss in anorexia nervosa: leptin, serotonin, and the sympathetic nervous system
Kumar, K. K., Tung, S., & Iqbal, J. Z. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05810.x · Cited by 27
Effects of Agouti‐Related Protein on Metabolism and Hypothalamic Neuropeptide Gene Expression
Körner, J., Wissig, S. L., Kim, A., Conwell, I. M., & Wardlaw, S. L. (2003) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2003.01113.x · Cited by 28
The Regulation of Feeding: A Cross Talk between Peripheral and Central Signalling
Brunetti, L., Nisio, C. D., Orlando, G., Ferrante, C., & Vacca, M. (2005) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200501800203 · Cited by 27
Proneth, B., Xiang, Z., Pogozheva, I. D., Litherland, S. A., Gorbatyuk, O. S., Shaw, A. M., Millard, W. J., Mosberg, H. I., & Haskell‐Luevano, C. (2006) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2006.00362.x · Cited by 27
“It has been shown that during chronic food restriction, mRNA levels encoding the orexigenic peptide AGRP are increased (8,21) and mRNA levels encoding the prohormone POMC of the anorexigenic peptide a-MSH are decreased in the hypothalamus (73,74).”
BackgroundMelanocortin-4 receptor: A novel signalling pathway involved in body weight regulation
Fisher, S., Yagaloff, K. A., & Burn, P. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0800796 · Cited by 27
Contribution of adaptive thermogenesis to the hypothalamic regulation of energy balance
Lage, R., Fernø, J., Nogueiras, R., Diéguez, C., & López, M. (2016) · Biochemical Journal · doi:10.1042/bcj20160012 · Cited by 28
Obesity, Metabolic Syndrome and Disorders of Energy Balance
Han, J. C., & Weiss, R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-62520-3.00024-5 · Cited by 27
Richard, D., & Baraboi, E. (2004) · Treatments in Endocrinology · doi:10.2165/00024677-200403050-00001 · Cited by 26
Iqbal, J., Pompolo, S., Dumont, L. M., Wu, C., Mountjoy, K. G., Henry, B. A., & Clarke, I. J. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00250-0 · Cited by 25
Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats
SUZUKI, Y., Nakahara, K., Maruyama, K., Okame, R., Ensho, T., Inoue, Y., & Murakami, N. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0015 · Cited by 24
Nam, J. S., Cho, M., Park, J. S., Ahn, C. W., Soo, B., Lee, E. J., Lim, S. K., Kim, K. R., & Lee, H. C. (2010) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2010.08.003 · Cited by 25
Melanin-concentrating hormone neuron system: the wide web that controls the feeding
Kawano, H., Honma, S., Honma, A., Horie, M., Kawano, Y., & Hayashi, S. (2002) · Anatomical Science International · doi:10.1046/j.0022-7722.2002.00027.x · Cited by 25
“intake ( Thornton et al ., 1997; Mizuno et al ., 1998; Kim et al ., 1996).”
Mizuno, T. M., Makimura, H., & Mobbs, C. V. (2003) · Annals of Medicine · doi:10.1080/07853890310012076 · Cited by 24
Metadata
- Authors
- Thornton, J. E., Cheung, C. C., Clifton, D. K., & Steiner, R. A.
- Affiliations
- University of Washington (US)
- Corresponding author
- Clifton, Donald K.
- ORCID
- Steiner, Robert A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1997-11-01
- Volume
- 138
- Issue
- 11
- Pages
- 5063-5066
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2064342369
- Cited by
- 437
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 12 · 2014: 9 · 2013: 12 · 2012: 9
- FWCI
- 12.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- ResearchWorks at the University of Washington (University of Washington) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 27142, P50HD012629, R01HD027142, P50-HD-12629)
- 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 mRNA, hypothalamus, arcuate nucleus, ob/ob mice, leptin receptor, melanocortin peptides, body weight regulation, reproduction, gene expression regulation
- MeSH terms
- Animals, Cell Count, Eating, Hypothalamus, Male, Mice, Mutant Strains, Neurons, Obesity, Pro-Opiomelanocortin, Proteins, RNA, Messenger, Leptin, Mice
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