The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway
| Autor: | Xiu-Ming Guo, Ding-Feng Su, Yun Tang, Yang Sun, Yili Yang, Zhen Qin, Xia Liu, Jinya Cai, Jing-Jing Wan |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Leptin Male STAT3 Transcription Factor medicine.medical_specialty Endocrinology Diabetes and Metabolism Hypothalamus Adipose tissue Orosomucoid Diet High-Fat Energy homeostasis Cell Line Rats Sprague-Dawley 03 medical and health sciences Eating Mice Internal medicine Internal Medicine medicine Animals Homeostasis Obesity Receptor Leptin receptor Leptin Deficiency biology Arcuate Nucleus of Hypothalamus Janus Kinase 2 Rats Mice Inbred C57BL 030104 developmental biology Endocrinology biology.protein Receptors Leptin Energy Metabolism Signal Transduction |
| Zdroj: | Diabetes. 65(6) |
| ISSN: | 1939-327X |
| Popis: | The acute-phase protein orosomucoid (ORM) exhibits a variety of activities in vitro and in vivo, notably modulation of immunity and transportation of drugs. We found in this study that mice lacking ORM1 displayed aberrant energy homeostasis characterized by increased body weight and fat mass. Further investigation found that ORM, predominantly ORM1, is significantly elevated in sera, liver, and adipose tissues from the mice with high-fat diet (HFD)–induced obesity and db/db mice that develop obesity spontaneously due to mutation in the leptin receptor (LepR). Intravenous or intraperitoneal administration of exogenous ORM decreased food intake in C57BL/6, HFD, and leptin-deficient ob/ob mice, which was absent in db/db mice and was significantly reduced in mice with arcuate nucleus (ARC) LepR knockdown, whereas enforced expression of ORM1 in ARC significantly decreased food intake, body weight, and serum insulin level. Furthermore, we found that ORM is able to bind directly to LepR and activate the receptor-mediated JAK2–STAT3 signaling in hypothalamus tissue and GT1-7 cells, which was derived from hypothalamic tumor. These data indicated that ORM could function through LepR to regulate food intake and energy homeostasis in response to nutrition status. Modulating the expression of ORM is a novel strategy for the management of obesity and related metabolic disorders. |
| Databáze: | OpenAIRE |
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