Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues.
Open accessAbstract
Leptin's effects are mediated by interactions with a receptor that is alternatively spliced, resulting in at least five different murine forms: Ob-Ra, Ob-Rb, Ob-Rc, Ob-Rd, and Ob-Re. A mutation in one splice form, Ob-Rb, results in obesity in mice. Northern blots, RNase protection assays, and PCR indicate that Ob-Rb is expressed at a relatively high level in hypothalamus and low level in several other tissues. Ob-Ra is expressed ubiquitously, whereas Ob-Rc, -Rd, and -Re RNAs are only detectable using PCR. In hypothalamus, Ob-Rb is present in the arcuate, ventromedial, dorsomedial, and lateral hypothalamic nuclei but is not detectable in other brain regions. These nuclei are known to regulate food intake and body weight. The level of Ob-Rb in hypothalamus is reduced in mice rendered obese by gold thioglucose (GTG), which causes hypothalamic lesions. The obesity in GTG-treated mice is likely to be caused by ablation of Ob-Rb-expressing neurons, which results in leptin resistance.
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ObRb is the only receptor isoform that expresses all the protein motifs required for cytokine receptor signaling.
“ObRb is the only receptor isoform that expresses all the protein motifs required for cytokine receptor signaling.”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [27]
ObRb was highly enriched in the hypothalamus in precisely those nuclei that alter body weight when lesioned.
“ObRb was highly enriched in the hypothalamus in precisely those nuclei that alter body weight when lesioned (25,27).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [27]
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- Authors
- Fei, H., Okano, H. J., Li, C., Lee, G.-H., Zhao, C., Darnell, R., & Friedman, J. M.
- Affiliations
- Laboratories of Molecular Genetics and Molecular Neurooncology, Rockefeller University, 1230 York Avenue, New York, NY 10021; and Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021
- Howard Hughes Medical Institute (US)
- Corresponding author
- Okano, Hirotaka J.
- Friedman, Jeffrey M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-06-24
- Volume
- 94
- Issue
- 13
- Pages
- 7001-7005
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC21274
- OpenAlex
- W2109311297
- Cited by
- 766
- References
- 28
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 19 · 2018: 14 · 2017: 24 · 2016: 27 · 2015: 24 · 2014: 29 · 2013: 37 · 2012: 25
- FWCI
- 15.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 09673-18, T32CA009673)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-41096, R01DK041096)
- National Institute of Neurological Disorders and Stroke (R01 NS34389, R01NS034389)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin receptor, Ob-Rb, alternative splicing, hypothalamus, arcuate nucleus, dorsomedial nucleus, lateral hypothalamic nucleus, ventromedial hypothalamus, gold thioglucose, hypothalamic lesions, obesity, leptin resistance, food intake regulation, body weight regulation, mouse brain
- MeSH terms
- Animals, Brain, Carrier Proteins, Molecular Sequence Data, Mutation, Organ Specificity, Receptors, Cell Surface, Blotting, Northern, Alternative Splicing, In Situ Hybridization, Mice, Receptors, Leptin
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