title: Human C-reactive protein impedes entry of leptin into the CNS and attenuates its physiological actions in the CNS.
abstract: Defective central leptin signalling and impaired leptin entry into the CNS (central nervous system) represent two important aspects of leptin resistance in obesity. In the present study, we tested whether circulating human CRP (C-reactive protein) not only diminishes signalling of leptin within the CNS, but also impedes this adipokine's access to the CNS. Peripheral infusion of human CRP together with co-infused human leptin was associated with significantly decreased leptin content in the CSF of ob/ob mice. Furthermore, following peripheral infusion of human leptin, the CSF (cerebrospinal fluid) concentration of leptin in transgenic mice overexpressing human CRP was sharply lower than that achieved in similarly infused wild-type mice. Administration of LPS (lipopolysaccharide) to human CRP-transgenic mice dramatically elevated the concentrations of human CRP in the CSF. The i.c.v. (intracerebroventricular) delivery of human CRP into the lateral ventricles of ob/ob mice blocked the satiety and weight-reducing actions of human leptin, but not those of mouse leptin. I.c.v. injection of human CRP abolished hypothalamic signalling by human leptin, and ameliorated the effects of leptin on the expression of NPY (neuropeptide Y), AgRP (Agouti-related protein), POMC (pro-opiomelanocortin) and SOCS-3 (suppressor of cytokine signalling 3). Human CRP can impede the access of leptin to the CNS, and elevation of human CRP within the CNS can have a negative impact on the physiological actions of leptin.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, U.S.A.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The Second People's Hospital of Chengdu, Chengdu, 610017, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.affiliation: Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCrory
authors.affiliation: Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education and Department of Clinical Biochemistry, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510640, China fli@njmu.edu.cn zjzhao@scut.edu.cn.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, School of Biological Sciences and Bioengineering, South China University of Technology, Guangzhou, Guangdong, 510640, China fli@njmu.edu.cn zjzhao@scut.edu.cn.
authors.forename: Allan Z
authors.initials: AZ
authors.lastname: Zhao
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D002097:C-Reactive Protein / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D020738:Leptin / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009478:Neuropeptide Y / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D021381:Protein Transport; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D020738:Leptin; D009478:Neuropeptide Y; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D011333:Pro-Opiomelanocortin; D002097:C-Reactive Protein
keywords: C-reactive protein; energy balance; leptin resistance; obesity