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Citations to this article

Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes
Carl de Luca, … , Shun-Mei Liu, Streamson C. Chua Jr.
Carl de Luca, … , Shun-Mei Liu, Streamson C. Chua Jr.
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3484-3493. https://doi.org/10.1172/JCI24059.
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Research Article Metabolism Article has an altmetric score of 10

Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes

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Abstract

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.

Authors

Carl de Luca, Timothy J. Kowalski, Yiying Zhang, Joel K. Elmquist, Charlotte Lee, Manfred W. Kilimann, Thomas Ludwig, Shun-Mei Liu, Streamson C. Chua Jr.

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 2 13 13 6 6 8 9 15 7 8 4 14 17 25 20 26 14 9 5 3 224
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2013 (17)

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Molecular Metabolism 2013
Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity
B Jayaram, W Pan, Y Wang, H Hsuchou, A Mace, GG Cornelissen-Guillaume, PK Mishra, RA Koza, AJ Kastin
Journal of applied physiology 2013
A critical view of the use of genetic tools to unveil neural circuits: the case of leptin action in reproduction
CF Elias
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2013
Diminished leptin signaling can alter circadian rhythm of metabolic activity and feeding
H Hsuchou, Y Wang, GG Cornelissen-Guillaume, AJ Kastin, E Jang, F Halberg, W Pan
Journal of applied physiology 2013
Adipocytes: impact on tumor growth and potential sites for therapeutic intervention
S Hefetz-Sela, PE Scherer
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Rif1 Prevents Resection of DNA Breaks and Promotes Immunoglobulin Class Switching
MD Virgilio, E Callen, A Yamane, W Zhang, M Jankovic, AD Gitlin, N Feldhahn, W Resch, TY Oliveira, BT Chait, A Nussenzweig, R Casellas, DF Robbiani, MC Nussenzweig
Science 2013
NHLH2: at the intersection of obesity and fertility
DJ Good, T Braun
Trends in Endocrinology & Metabolism 2013
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MH Donovan, LH Tecott
Frontiers in neuroscience 2013
Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis
V Nordström, M Willershäuser, S Herzer, J Rozman, OB Halbach, S Meldner, U Rothermel, S Kaden, FC Roth, C Waldeck, N Gretz, MH de Angelis, A Draguhn, M Klingenspor, HJ Gröne, R Jennemann
PLoS Biology 2013
In vivo characterization of the role of tissue-specific translation elongation factor 1A2 in protein synthesis reveals insights into muscle atrophy
J Doig, LA Griffiths, D Peberdy, P Dharmasaroja, M Vera, FJ Davies, HJ Newbery, D Brownstein, CM Abbott
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Proceedings of the National Academy of Sciences 2013
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PloS one 2013
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American journal of physiology. Endocrinology and metabolism 2013
Investigating the Role of Tbx4 in the Female Germline in Mice
NC Douglas, R Arora, CY Chen, MV Sauer, VE Papaioannou
Biology of reproduction 2013
A General Approach for Controlling Transcription and Probing Epigenetic Mechanisms: Application to the Cd4 Locus
M Wan, R Kaundal, H Huang, J Zhao, X Yang, BH Chaiyachati, S Li, T Chi
Journal of immunology (Baltimore, Md. : 1950) 2013
Melanocortin-3 Receptors and Metabolic Homeostasis
Begriche K, Girardet C, McDonald P, Butler AA
Progress in molecular biology and translational science 2013

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