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Adiponectin and Resistin in Human Cerebrospinal Fluid and Expression of Adiponectin Receptors in the Human Hypothalamus

University of Warwick (K.K., A.L.H., N.F.d.S., J.P.O., P.G.M., S.K.), Unit for Diabetes and Metabolism, Clinical Sciences Research Institute, Coventry CV2 2DX, United Kingdom; Department of Forensic Medicine and Department of Clinical Pathology (A.T., G.C.), Varna Medical University, Varna 9002, Bulgaria; Department of Histopathology (S.J., D.R.S.), University Hospital of Coventry and Warwickshire National Health Service (NHS) Trust, Coventry CV2 2DX, United Kingdom; and Department of Anaesthetics (B.H.), Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham B9 5SS, United Kingdom

Address all correspondence and requests for reprints to: Professor Sudhesh Kumar, University of Warwick, Clinical Sciences Research Institute, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, United Kingdom. E-mail: Sudhesh.Kumar{at}warwick.ac.uk.

Context: 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/m²; women, 27.3 ± 4.8 kg/m²) 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.

Conclusion: 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.

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