| Signaling through Tyr985 of leptin receptor as an age/diet-dependent switch in the regulation of energy balance. | |
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MedLine Citation:
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PMID: 20086094 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Leptin regulates energy homeostasis through central activation of multiple signaling pathways mediated by Ob-Rb, the long form of leptin receptor. Leptin resistance underlies the pathogenic development of obesity, which is closely associated with environmental factors. To further understand the physiological function of leptin signaling mechanisms, we generated a knock-in line of mice (Y985F) expressing a mutant Ob-Rb with a phenylalanine substitution for Tyr985, one of the three intracellular tyrosines that mediate leptin's signaling actions. Surprisingly, whereas young homozygous Y985F animals were slightly leaner, they exhibit adult-onset or diet-induced obesity. Importantly, both age-dependent and diet-induced deterioration of energy balance was paralleled with pronounced leptin resistance, which was largely attributable to attenuation of leptin-responsive hypothalamic STAT3 activation as well as prominently elevated expression of hypothalamic SOCS3, a key negative regulator of leptin signaling. Thus, these results unmask distinct binary roles for Try985-mediated signaling in energy metabolism, acting as an age/diet-dependent regulatory switch to counteract age-associated or diet-induced obesity. |
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Authors:
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Jia You; Yue Yu; Lei Jiang; Wenxia Li; Xinxin Yu; Lety Gonzalez; Guoqing Yang; Zunji Ke; Wenjun Li; Cai Li; Yong Liu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-19 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-09 Completed Date: 2010-04-09 Revised Date: 2010-10-04 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1650-9 Citation Subset: IM |
Affiliation:
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Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology* Animals Diet Dietary Fats / metabolism Eating Energy Metabolism / physiology* Female Gene Knock-In Techniques Humans Hypothalamus / metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Neuropeptides / genetics, metabolism Obesity / metabolism, physiopathology Receptors, Leptin / genetics, metabolism* STAT3 Transcription Factor / metabolism Signal Transduction / physiology* Suppressor of Cytokine Signaling Proteins / genetics, metabolism Tyrosine / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Neuropeptides; 0/Receptors, Leptin; 0/STAT3 Transcription Factor; 0/Socs3 protein, mouse; 0/Suppressor of Cytokine Signaling Proteins; 55520-40-6/Tyrosine |
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