The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Identification of targets of leptin action in rat hypothalamus.
Open accessAbstract
The hypothesis that leptin (OB protein) acts in the hypothalamus to reduce food intake and body weight is based primarily on evidence from leptin-deficient, ob/ob mice. To investigate whether leptin exerts similar effects in normal animals, we administered leptin intracerebroventricularly (icv) to Long-Evans rats. Leptin administration (3.5 microg icv) at the onset of nocturnal feeding reduced food intake by 50% at 1 h and by 42% at 4 h, as compared with vehicle-treated controls (both P < 0.05). To investigate the basis for this effect, we used in situ hybridization (ISH) to determine whether leptin alters expression of hypothalamic neuropeptides involved in energy homeostasis. Two injections of leptin (3.5 microg icv) during a 40 h fast significantly decreased levels of mRNA for neuropeptide Y (NPY, which stimulates food intake) in the arcuate nucleus (-24%) and increased levels of mRNA for corticotrophin releasing hormone (CRH, an inhibitor of food intake) in the paraventricular nucleus (by 38%) (both P < 0.05 vs. vehicle-treated controls). To investigate the anatomic basis for these effects, we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants. Leptin receptor mRNA was densely concentrated in the arcuate nucleus, with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance. These findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.
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Citations
Cites
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Self-citationAbnormal splicing of the leptin receptor in diabetic mice
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“This hypothesis is supported by the observation that leptin treatment lowers NPY mRNA levels in the arcuate nucleus of ob/ob mice (14, 15).”
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“NPY genes, as described elsewhere (16, 25).”
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Cited by
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
A role for ghrelin in the central regulation of feeding
Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., & Matsukura, S. (2001) · Nature · doi:10.1038/35051587 · Cited by 3,443
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170
Pathophysiology of migraine: a disorder of sensory processing
Goadsby, P. J., Holland, P. R., Martins-Oliveira, M., Hoffmann, J., Schankin, C., & Akerman, S. (2017) · Physiological Reviews · doi:10.1152/physrev.00034.2015 · Cited by 1,998
The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review
Klok, M. D., Jakobsdottir, S., & Drent, M. L. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2006.00270.x · Cited by 1,442
Metadata
- Authors
- Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G.
- Venue
- Journal of Clinical Investigation
- Published
- 1996-09-01
- Volume
- 98
- Issue
- 5
- Pages
- 1101-1106
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2111232488
- Cited by
- 1,496
- References
- 9
- FWCI
- 33.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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