title: The Acute-Phase Protein Orosomucoid Regulates Food Intake and Energy Homeostasis via Leptin Receptor Signaling Pathway.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Translational Medicine, Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Jinya
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Guo
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China lxflying@aliyun.com dfsu@smmu.edu.cn.
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China lxflying@aliyun.com dfsu@smmu.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009961:Orosomucoid / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000172:deficiency / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020738:Leptin; D009961:Orosomucoid; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2