The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes
Open accessAbstract
We have generated mice that carry a neuron-specific leptin receptor (LEPR) transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR B (SYN-LEPR-B). We have also generated mice that are compound hemizygotes for the transgenes SYN-LEPR-B and neuron-specific enolase-LEPR B (NSE-LEPR-B). We observed a degree of correction in db/db mice that are hemizygous (Syn db/db) and homozygous (Syn/Syn db/db) for the SYN-LEPR-B transgene similar to that previously reported for the NSE-LEPR-B transgene. We also show complete correction of the obesity and related phenotypes of db/db mice that are hemizygous for both NSE-LEPR-B and SYN-LEPR-B transgenes (Nse+Syn db/db). Body composition, insulin sensitivity, and cold tolerance were completely normalized in Nse+Syn db/db mice at 12 weeks of age compared with lean controls. In situ hybridization for LEPR B isoform expression in Nse+Syn db/db mice showed robust expression in the energy homeostasis-relevant regions of the hypothalamus. Expression of 3 neuropeptide genes, agouti-related peptide (Agrp), neuropeptide Y (Npy), and proopiomelanocortin (Pomc), was fully normalized in dual transgenic db/db mice. The 2 transgenes in concert conferred normal fertility to male and female db/db mice. Male mice with partial peripheral deletion of Lepr, induced in the periweaning phase, did not show alterations in body composition or mass. In summary, we show that brain-specific leptin signaling is sufficient to reverse the obesity, diabetes, and infertility of db/db mice.
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Citations
Cites
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Self-citationSTAT3 signalling is required for leptin regulation of energy balance but not reproduction
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Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis
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Self-citation
Cited by
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
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The Human Obesity Gene Map: The 2005 Update
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Adipokines as novel biomarkers and regulators of the metabolic syndrome
Deng, Y., & Scherer, P. E. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05875.x · Cited by 558
Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons
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Metadata
- Authors
- de Luca, C., Kowalski, T. J., Zhang, Y., Elmquist, J. K., Lee, C., Kilimann, M. W., Ludwig, T., Liu, S.-M., & Chua, S. C.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-12-01
- Volume
- 115
- Issue
- 12
- Pages
- 3484-3493
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2144219438
- Cited by
- 383
- References
- 36
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- bronze
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- de Luca, C., Kowalski, T. J., Zhang, Y., Elmquist, J. K., Lee, C., Kilimann, M. W., Ludwig, T., Liu, S.-M., & Chua, S. C. (2005). Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. Journal of Clinical Investigation. https://doi.org/10.1172/jci24059
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