The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset
Abstract
Rats selectively bred to develop diet-induced obesity (DIO) were compared with those bred to be diet resistant (DR) on a 31% fat high-energy diet with regard to their central leptin signaling and blood-brain barrier (BBB) transport. Peripheral leptin injection (15 mg/kg ip) into lean 4- to 5-wk-old rats produced 54% less anorexia in DIO than DR rats. DIO rats also had 21, 63, and 64% less leptin-induced immunoreactive phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expression in the hypothalamic arcuate, ventromedial, and dorsomedial nuclei, respectively. However, hindbrain leptin-induced nucleus tractus solitarius pSTAT3 and generalized sympathetic (24-h urine norepinephrine) activation were comparable. Reduced central leptin signaling was not due to defective BBB transport since transport did not differ between lean 4- to 5-wk-old DIO and DR rats. Conversely, DIO leptin BBB transport was reduced when they became obese at 23 wk of age on low-fat chow or after 6 wk on high-energy diet. In addition, leptin receptor mRNA expression was 23% lower in the arcuate nuclei of 4- to 5-wk-old DIO compared with DR rats. Thus a preexisting reduction in hypothalamic but not brain stem leptin signaling might contribute to the development of DIO when dietary fat and caloric density are increased. Defects in leptin transport appear to be an acquired defect associated with the development of obesity and possibly age.
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Cites
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BackgroundTwo defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity
El-Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjørbæk, C., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9842 · Cited by 887
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The Concept of Selective Leptin Resistance
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Cited by
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
Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737
Molecular and anatomical determinants of central leptin resistance
Münzberg, H., & Myers, M. G. (2005) · Nature Neuroscience · doi:10.1038/nn1454 · Cited by 550
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Recinella, L., Orlando, G., Ferrante, C., Chiavaroli, A., Brunetti, L., & Leone, S. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.578966 · Cited by 261
Metadata
- Authors
- Levin, B. E., Dunn-Meynell, A. A., & Banks, W. A.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2004-01
- Volume
- 286
- Issue
- 1
- Pages
- R143-R150
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W1992328870
- Cited by
- 270
- References
- 9
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- closed
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- Levin, B. E., Dunn-Meynell, A. A., & Banks, W. A. (2004). Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. https://doi.org/10.1152/ajpregu.00393.2003
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