CTRP-3 is permeable to the blood-brain barrier and is not regulated by glucose or lipidsin vivo

Background C1q/TNF-related protein-3 (CTRP-3) represents a novel anti-inflammatory and anti-diabetic 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 Aim 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 Material and 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 x 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. This article is protected by copyright. All rights reserved.