Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus.
BACKGROUND
The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier.


OBJECTIVE
The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin. Furthermore, we wished to examine the expression of the adiponectin receptors 1 and 2 (AdipR1, AdipR2) in the human hypothalamus.


METHODS
For this purpose, serum and CSF samples were collected from 20 men and 19 women matched for age [men, 69.8 +/- 8.6 yr (mean +/- SD); women, 69.4 +/- 4.3 yr] and BMI (men, 29.4 +/- 3.4 kg/m(2); women, 27.3 +/- 4.8 kg/m(2)) undergoing elective surgery under spinal anesthesia.


RESULTS
Adiponectin was identified in CSF with levels 1000-fold less than serum, whereas resistin and leptin levels were 100-fold less. Unlike their serum levels, adiponectin CSF levels showed no gender difference or correlation with insulin resistance, which is similar to resistin CSF levels. The adiponectin and leptin CSF/serum ratios in our study exhibit the same pattern of gender-specific BMI association with inverse correlation in women (r = -0.61; P = 0.02) and no correlation in men (r = 0.026; P = not significant). Furthermore, immunostaining established AdipR1 and -2 in the hypothalamus and increased AdipR2 expression in the paraventricular nucleus, which is involved in energy regulation.


CONCLUSIONS
In summary, our findings show both the presence of adiponectin and resistin in human CSF, with no effect of insulin resistance on CSF levels. The CSF entry of adiponectin and leptin in women appears to be impaired in obesity.
Kos
Katarina
K
University of Warwick, Clinical Sciences Research Institute, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, United Kingdom.
Harte
Alison L
AL
da Silva
Nancy F
NF
Tonchev
Anton
A
Chaldakov
Georgi
G
James
Sean
S
Snead
David R
DR
Hoggart
Barbara
B
O'Hare
Joseph P
JP
McTernan
Philip G
PG
Kumar
Sudhesh
S
D052242:Adiponectin / Q000097:blood / Q000134:cerebrospinal fluid*; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D052243:Resistin / Q000097:blood / Q000134:cerebrospinal fluid*
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D020738:Leptin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D052243:Resistin