Quantification and regulation of the adipokines resistin and progranulin in human cerebrospinal fluid.
BACKGROUND
Adipokines bearing the potential to cross the blood-brain barrier (BBB) are promising candidates for the endocrine regulation of central nervous processes and of a postulated fat-brain axis. Resistin and progranulin concentrations in paired serum and cerebrospinal fluid (CSF) samples of patients undergoing neurological evaluation and spinal puncture were investigated.


METHODS
Samples of n = 270 consecutive patients with various neurological diseases were collected without prior selection. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay and serum and CSF routine parameters by standard procedures. Anthropometric data, medication and patient history were available.


RESULTS
Serum levels of resistin and progranulin were positively correlated among each other, with respective CSF levels, low-density lipoprotein cholesterol levels and markers of systemic inflammation. CSF resistin concentrations were generally low. Progranulin CSF concentrations and CSF/serum progranulin ratio were significantly higher in patients with infectious diseases, with disturbed BBB function and with elevated CSF cell count and presence of oligoclonal bands. Both adipokines are able to cross the BBB depending on a differing patency that increases with increasing grade of barrier dysfunction. Whereas resistin represents a systemic marker of inflammation, CSF progranulin levels strongly depend on the underlying disease and dysfunction of blood-CSF barrier.


CONCLUSIONS
Resistin and progranulin represent novel and putative regulators of the fat-brain axis by their ability to cross the BBB under physiological and pathophysiological conditions. The presented data provide insight into the characteristics of BBB function regarding progranulin and resistin and the basis for future establishment of normal values for CSF concentrations and CSF/serum ratios.
Department of Neurology, Giessen University Hospital, Giessen, Germany.
Martin
M
Berghoff
Department of Internal Medicine III, Giessen University Hospital, Giessen, Germany.
Alexandra
A
Hochberg
Department of Internal Medicine III, Giessen University Hospital, Giessen, Germany.
Andreas
A
Schmid
Department of Internal Medicine III, Giessen University Hospital, Giessen, Germany.
Jutta
J
Schlegel
Department of Internal Medicine III, Giessen University Hospital, Giessen, Germany.
Thomas
T
Karrasch
Department of Neurology, Giessen University Hospital, Giessen, Germany.
Manfred
M
Kaps
Department of Internal Medicine III, Giessen University Hospital, Giessen, Germany.
Andreas
A
Schäffler
D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000378:metabolism; D015992:Body Mass Index; D002452:Cell Count; D002494:Central Nervous System Infections / Q000134:cerebrospinal fluid*; D002561:Cerebrovascular Disorders / Q000134:cerebrospinal fluid*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003389:Cranial Nerve Diseases / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000134:cerebrospinal fluid; D005157:Facial Pain / Q000134:cerebrospinal fluid; D005260:Female; D006261:Headache / Q000134:cerebrospinal fluid; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D000077153:Progranulins; D052243:Resistin / Q000097:blood / Q000134:cerebrospinal fluid*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; C499624:RETN protein, human; D052243:Resistin; D014280:Triglycerides; D002784:Cholesterol
Adipokines; cerebrospinal fluid; inflammation; progranulin; resistin