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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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- [11]11. Mercer JG, Hoggard N, Williams LM, Lawrence CB, Hannah LT, Trayhurn P 1996 Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Letters 387:113-116.
- [22]22. Cheung CC, Clifton DK, Steiner RA in press Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology
- [29]29. Franklin KBJ, Paxinos G 1997 The mouse brain in stereotaxic coordinates, Ed., Academic Press,
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“Although inconsistent with a recent report (387), leptin injections to leptin-deficient ob/ob mice suppressed POMC mRNA (363).”
BackgroundSignals That Regulate Food Intake and Energy Homeostasis
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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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