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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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“Leptin receptors are found on ARC POMC neurons (Cheung et al., 1997), POMC expression in the ARC is increased by leptin (Schwartz et al., 1997; Thornton et al., 1997; Mizuno et al., 1998), and when CNS MC receptors are antagonized, the ability of leptin to inhibit food intake is abolished (Seeley et al., 1997b).”
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“The melanocortin (MC) pathway is important for the regulation of energy homeostasis, as revealed by genetic and pharmacological evidence (9–16), and MCs are an important target of leptin action within the brain (17,18).”
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“The localization of leptin-induced phospho-STAT3 immunoreactive cells in the Arc, VMH, and LHA, all of which are known to regulate feeding behavior, adds further evidence in support of hypothalamic sites of leptin’s action.”
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“…in the hypothalamus involves the altered expression of hypothalamic neuropeptides (Ahima et al. 1996; Légrádi et al. 1997; Quintela et al. 1997; Thornton et al. 1997; Mizuno et al. 1998; Sahu 1998), including NPY mRNA (Schwartz et al. 1996a–c,1998) and pro-opiomelanocortin mRNA (Schwartz et…”
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Physiological and Anatomical Circuitry between Agouti-Related Protein and Leptin Signaling
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Leptin Is an Endogenous Protective Protein against the Toxicity Exerted by Tumor Necrosis Factor
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“POMC neurons in the arcuate nucleus are known to express receptors for leptin (Cheung et al., 1997) and insulin (Benoit et al., 2002), and binding of leptin and insulin increases POMC gene expression (Schwartz et al., 1997; Thornton et al., 1997; Benoit et al., 2002).”
BackgroundCharacterization of Agouti-Related Protein Binding to Melanocortin Receptors
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Separate systems for serotonin and leptin in appetite control
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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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“, 1999), while obese, leptin-deficient ob/ob mice show reduced POMC mRNA expression in the ARC, which can be rescued by leptin administration (Thornton et al., 1997).”
BackgroundThe role of leptin in health and disease
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“Leptin downregulates NPY/AgRP mRNA expression (1, 33, 36) and upregulates POMC mRNA expression (34, 40).”
BackgroundDown regulation of the prepro-orexin gene expression in genetically obese mice
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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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