title: CTRP-3 is permeable to the blood-brain barrier and is not regulated by glucose or lipids in vivo.
abstract: BACKGROUND
  C1q/TNF-related protein-3 (CTRP-3) represents a novel anti-inflammatory and antidiabetic adipokine secreted by adipose tissue. The physiological and postprandial regulation of CTRP-3 remains obscure and it is not known whether CTRP-3 is permeable to the brain. The postprandial regulation of CTRP-3 during an oral glucose tolerance test (n = 100) and an oral lipid tolerance test (n = 100) in humans was investigated. Moreover, CTRP-3 concentrations were measured in paired serum and cerebrospinal fluid (CSF) samples of patients (n = 270) undergoing neurological evaluation. The expression of CTRP-3 mRNA was investigated in adipocytes upon stimulation with glucose, sex hormones and a broad panel of fatty acids.
  
  
  METHODS
  Serum and CSF CTRP-3 concentrations were measured by ELISA. 3T3-L1 adipocytes were used for stimulation experiments. CTRP-3 mRNA expression was quantified by using real-time PCR analysis.
  
  
  RESULTS
  CTRP-3 is present in human cerebrospinal fluid with a mean CSF/serum ratio of 110 ± 64 × 10-3. CTRP-3 is not regulated postprandially by carbohydrates or lipids in the healthy state. Females have slightly higher levels of CTRP-3 when compared to males. A significant and positive correlation of CTRP-3 to LDL cholesterol serum levels is reproducible in several cohorts and deserves further mechanistic investigation. Whereas glucose concentrations do not influence CTRP-3 mRNA expression in 3T3-L1 adipocytes in vitro, fatty acids differentially modulate CTRP-3 expression.
  
  
  CONCLUSIONS
  The novel adipokine CTRP-3 is detectable in human cerebrospinal fluid (proof of principle). Due to its blood-brain barrier permeability, CTRP-3 represents a novel putative candidate for a physiological regulator molecule affecting central nervous functions.
authors.affiliation: Department of Internal Medicine III, University Hospital Giessen, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmid
authors.affiliation: Department of Neurology, University Hospital Giessen, Giessen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Berghoff
authors.affiliation: Department of Internal Medicine III, University Hospital Giessen, Giessen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hochberg
authors.affiliation: Department of Internal Medicine III, University Hospital Giessen, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäffler
authors.affiliation: Department of Internal Medicine III, University Hospital Giessen, Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Karrasch
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D002463:Cell Membrane Permeability / Q000187:drug effects*; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D048069:Tumor Necrosis Factors / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C506069:C1QTNF3 protein, human; D008055:Lipids; D048069:Tumor Necrosis Factors; D005947:Glucose
keywords: Adipocyte; CTRP-3; adipokine; blood-brain barrier; cerebrospinal fluid; lipid tolerance test