Leptin Increases Hypothalamic Pro-opiomelanocortin mRNA Expression in the Rostral Arcuate Nucleus
Open accessAbstract
Melanocortins are peptides, cleaved from the pro-opiomelanocortin (POMC) precursor, that act in the brain to reduce food intake and are potential mediators of leptin action. In the forebrain, melanocortins are derived from POMC-containing neurons of the hypothalamic arcuate nucleus. To test the hypothesis that these POMC neurons are regulated by leptin, we used in situ hybridization to determine whether reduced leptin signaling (as occurs in fasting), genetic leptin deficiency (in obese ob/ob mice), or genetic leptin resistance (in obese db/db mice) lower expression of POMC mRNA. We further hypothesized that leptin administration would raise hypothalamic POMC mRNA levels in leptin-deficient animals, but not in mice with defective leptin receptors. In wild-type mice (n = 12), fasting for 48 h lowered POMC mRNA levels in the rostral arcuate nucleus by 53%, relative to values in fed controls (n = 8; P < 0.001). Similarly, arcuate nucleus POMC mRNA levels were reduced by 46 and 70% in genetically obese ob/ob (n = 6) and db/db mice (n = 6), respectively, as compared with wild-type mice (n = 5) (P < 0.01 for both comparisons). Five daily intraperitoneal injections of recombinant murine leptin (150 μg) raised levels of POMC mRNA in the rostral arcuate nucleus of ob/ob mice (n = 8) by 73% over saline-treated ob/ob control values (n = 8; P < 0.01), but was without effect in db/db mice (n = 6). In normal rats, two injections of a low dose of leptin (3.5 μg) into the third cerebral ventricle (n = 15) during a 40-h period of fasting also increased POMC mRNA levels in the rostral arcuate nucleus to values 39% greater than those in vehicle-treated controls (n = 14; P = 0.02). We conclude that reduced central nervous system leptin signaling owing to fasting or to genetic defects in leptin or its receptor lower POMC mRNA levels in the rostral arcuate nucleus. The finding that leptin reverses this effect in ob/ob, but not db/db, mice suggests that leptin stimulates arcuate nucleus POMC gene expression via a pathway involving leptin receptors. These findings support the hypothesis that leptin signaling in the brain involves activation of the hypothalamic melanocortin system.
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POMC neurons are stimulated by leptin.
“POMC neurons are stimulated by leptin (33, 162)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [162]
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- Seeley RJ, Thiele TE, van Dyk G, Baskin DG, Yagaloff KA, Fisher SL, Burn P, Schwartz MW: The hypothalamic melanocortin system is an important medi- ator of leptin's effect on food intake and body weight. Nature, hi press
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- Authors
- Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., & Baskin, D. G.
- Affiliations
- University of Washington (US)
- Department of Metabolic Diseases, Hoffmann-LaRoche Nutley, New Jersey
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1997-12-01
- Volume
- 46
- Issue
- 12
- Pages
- 2119-2123
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2016261339
- Cited by
- 879
- References
- 21
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 23 · 2020: 20 · 2019: 20 · 2018: 11 · 2017: 16 · 2016: 17 · 2015: 21 · 2014: 27 · 2013: 36 · 2012: 27
- FWCI
- 16.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- leptin, proopiomelanocortin, arcuate nucleus, hypothalamus, melanocortin peptides, leptin resistance, leptin receptor, ob/ob mice, db/db mice, fasting, food intake regulation, leptin signaling, obesity, intracerebroventricular administration, gene expression regulation, neuropeptides
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Drug Resistance, Fasting, Hypothalamus, Injections, Intraperitoneal, Injections, Intraventricular, Male, Pro-Opiomelanocortin, Proteins, RNA, Messenger, Gene Expression, In Situ Hybridization, Leptin, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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