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

2007 ◽  
Vol 92 (3) ◽  
pp. 1129-1136 ◽  
Author(s):  
Katarina Kos ◽  
Alison L. Harte ◽  
Nancy F. da Silva ◽  
Anton Tonchev ◽  
Georgi Chaldakov ◽  
...  

Abstract 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.

Author(s):  
Alexandra Höpfinger ◽  
Martin Berghoff ◽  
Thomas Karrasch ◽  
Andreas Schmid ◽  
Andreas Schäffler

Abstract 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.


Author(s):  
Xin Liao ◽  
Sha Liu ◽  
Xuejiao Tang ◽  
Dan Yang ◽  
Hua Liu ◽  
...  

Abstract Aims CTRP6, a newly discovered adipokine, has been found to be a regulator for energy homeostasis. However, the association between circulating CTRP6 and obesity in humans is still unclear. Methods 256 individuals, including 185 overweight/obese (OW/OB) and 71 normal weight adults, were recruited for this study. Circulating concentrations of CTRP6 and adiponectin (Adipoq) were examined by ELISA. Results Serum CTRP6 levels in obese individuals were significantly increased compared with those in healthy individuals (506.1±134.9 vs.363.3±80.5 ng/mL, P<0.01). Conversely, serum Adipoq concentrations in OW/OB individuals were markedly decreased compared with healthy controls [20.8 (12.1–29.3) vs. 14.1 ( 8.61–17.7) ; P<0.01]. Correlation analysis revealed that there was a positive relationship between circulating CTRP6 and age, BMI, Fat%, LDL-C, TG, WHR, TC, FBG, FIns, HOMA-IR and HbA1c, but there was an inverse correlation with Adipoq and HDL-C. Logistic regression analysis revealed that high serum CTRP6 levels are markedly associated with OW/OB. Finally, ROC curve analysis showed that the cut-off value for serum CTRP6 for prediction of IR is 518 ng/mL. Conclusions CTRP6 may be a marker related to OW/OB.


2021 ◽  
Vol 10 (15) ◽  
pp. 3271
Author(s):  
Martin Berghoff ◽  
Alexandra Höpfinger ◽  
Ranjithkumar Rajendran ◽  
Thomas Karrasch ◽  
Andreas Schmid ◽  
...  

Data on the quantification of the potentially neurotrophic adipo-myokine METRNL (Meteorin-like protein) in human cerebrospinal fluid (CSF) are lacking and migration of this secreted protein across the blood–brain barrier (BBB) is uncertain. In the present pilot study, METRNL concentrations were quantified by ELISA in paired serum and CSF samples of 260 patients (107 males, 153 females) undergoing neurological evaluation. METRNL was abundant in serum (801.2 ± 378.3 pg/mL) and CSF (1007.2 ± 624.2 pg/mL) with a CSF/serum ratio of 1.4 ± 0.8. Serum METRNL levels were significantly correlated (rho = +0.521) to those in CSF. CSF METRNL concentrations were significantly correlated (rho = +0.480) with albumin CSF/serum ratios. The CSF/serum ratios of METRNL and albumin were positively correlated in Reibergram analysis (rho = 0.498), indicating that raising CSF concentrations of METRNL are mediated by increasing BBB dysfunction. The CSF concentrations of METRNL strongly increased in a stepwise manner along with increasing BBB dysfunction from grade 0 to grade 3 and with rising CSF cell count. CSF/serum ratio of METRNL also increased from grade 0 (1.2 ± 0.7) to grade 3 (3.0 ± 0.2). Furthermore, CSF levels were positively correlated with age. In conclusion, METRNL is a secreted and neurotrophic myokine that crosses over the BBB. CSF concentrations of METRNL increase with BBB dysfunction.


2013 ◽  
Vol 119 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Bin Zhang ◽  
Ming Tian ◽  
Hui Zheng ◽  
Yu Zhen ◽  
Yun Yue ◽  
...  

Abstract Background: Accumulation of β-amyloid protein (Aβ) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase Aβ levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of Aβ and tau in humans. Methods: The participants were assigned into spinal anesthesia (N = 35), spinal plus desflurane anesthesia (N = 33), or spinal plus isoflurane anesthesia (N = 38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of Aβ (Aβ40 and Aβ42) and total tau in the CSF were determined. Results: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF Aβ40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P = 0.022. Desflurane, but not isoflurane, was associated with a decrease in Aβ42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P = 0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. Conclusions: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF Aβ levels.


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