CONTEXT: Data on the presence/quantification of the neurotrophic adipokines 
retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived 
factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of 
these adipokines across of the blood-brain barrier (BBB) is uncertain.
OBJECTIVE: This work aimed to quantify RBP4, PEDF, and clusterin in paired serum 
and CSF samples of patients undergoing neurological evaluation.
METHODS: A total of 268 patients (109 male, 159 female) were included. Adipokine 
serum and CSF concentrations were measured by enzyme-linked immunosorbent assay 
in duplicate.
RESULTS: RBP4 was abundant in serum (mean, 31.9 ± 24.2 μg/mL). The serum 
concentrations were approximately 145 times higher than in CSF (CSF to serum 
RBP4 ratio, 8.2 ± 4.3 × 10-3). PEDF was detectable in serum (mean, 30.2 ± 11.7 
μg/mL) and concentrations were approximately 25 times higher than in CSF (CSF to 
serum PEDF ratio, 42.3 ± 15.6 × 10-3). Clusterin serum concentrations were 
abundant with mean levels of 346.0 ± 114.6 μg/mL, which were approximately 40 
times higher than CSF levels (CSF to serum clusterin ratio, 29.6 ± 23.4 × 10-3). 
RBP4 and PEDF serum levels correlated positively with CSF levels, which were 
increased in overweight/obese patients and in type 2 diabetic patients. The CSF 
concentrations of all 3 adipokines increased with BBB dysfunction. RBP4 in CSF 
correlated positively with inflammatory parameters. In detail, only RBP4 showed 
the kinetics and associations that are mandatory for a putative mediator of the 
fat-brain axis.
CONCLUSION: RBP4, PEDF, and clusterin are permeable to the BBB and increase with 
the measure of BBB dysfunction. RBP4 represents an inflammatory neurotrophic 
adipokine and is a promising mediator of the fat-brain axis.