Increased resistin levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica.

INTRODUCTION: Resistin, which acts as a pro-inflammatory cytokine, has been implicated in the pathogenesis of several autoimmune diseases. However, the involvement of resistin in neuromyelitis optica (NMO), a severe inflammatory central nervous system disorder that targets the optic nerve and spinal cord, remains unclear. METHODS: We measured serum and cerebrospinal fluid (CSF) resistin levels in patients with NMO and controls matched by age and sex. The link between resistin levels and clinical variables in NMO was subsequently assessed. RESULTS: The concentrations of serum and CSF resistin were significantly higher in patients with NMO than in controls, and decreased following treatment with methylprednisolone. High sensitivity C-reactive protein (hs-CRP) levels and annualized relapse rate positively correlated with resistin levels in patients with NMO. CONCLUSION: Resistin might be a useful biomarker of inflammation in NMO, and a potential target for the treatment of NMO.

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. MATERIALS AND 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.

Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?

INTRODUCTION: Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients. METHODS: In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF). RESULTS: Baseline FIQ fatigue correlated negatively with serum leptin (r=-0.345; P=0.016) and nerve growth factor (NGF; r=-0.412; P=0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r=-0.694; P=0.038). FIQ Fatigue associated negatively with CSF resistin (r=-0.365; P=0.073). Similarly, FIQ fatigue (r=-0.444; P=0.026) and MFIGF correlated negatively with CSF adiponectin (r=-0.508; P=0.01). In lean patients, FIQ fatigue (P=0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P=0.017), overweight (MFIGF: P=0.001), and obese patients (MFIGF: P=0.016). After 15 weeks, total IGF-1 increased in lean (P=0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P=0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r=-0.329; P=0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r=-0.463; P=0.034) and positively with ∆neuropeptide Y (NPY) (r=0.469; P=0.032). Resistin increased after 30 weeks (P=0.034). ∆MFIGF correlated negatively with ∆resistin (r=-0.346; P=0.031), being strongest in obese patients (r=-0.815; P=0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r=-0.711; P=0.032). CONCLUSIONS: Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00643006.

Concentrations of hormones and metabolites in cerebrospinal fluid and plasma of dairy cows during the periparturient period.

During early lactation, high-yielding dairy cows often show insufficient feed intake (FI) and, as a consequence, they enter into a negative energy balance associated with an altered pattern of plasma metabolites and hormones. These act as short- and long-term hunger or satiety signals in the brain and play an important role in the control of FI. Metabolites and hormones also occur in cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem, 2 major centers of FI regulation. The CSF hormone and metabolite concentrations are mainly under control of the blood-brain barrier. Consequently, CSF hormone and metabolite concentrations differ from those in blood. However, the contribution of putative orexigenic and anorexigenic CSF signals possibly leading to insufficient FI of high-yielding dairy cows during early lactation has not been studied so far. Therefore, the aim of this study was to elucidate associations existing between both plasma and CSF hormones and metabolites during the periparturient period. Ten multiparous German Holstein dairy cows were fed ad libitum and samples of CSF from the spinal cord and blood from the jugular vein were withdrawn before morning feeding on d -20, -10, +1, +10, +20, and +40 relative to calving. Feed intake started to decrease from d 5 before calving and increased thereafter. Glucose, ß-hydroxybutyrate (BHBA), cholesterol, nonesterified fatty acids, urea (all enzymatic), lactate (colorimetric), amino acids (HPLC), osmolality (osmometer), ghrelin (RIA), leptin (ELISA), and resistin (Western immunoblot) were measured in both CSF and plasma, whereas free fatty acids (gas chromatography-mass spectrometry) and volatile fatty acids (gas chromatography-flame-ionization detector) were determined in plasma only. Whereas leptin concentrations decreased after calving in both plasma and CSF, ghrelin concentrations were not altered, and abundances of total resistin and its hexamers decreased only in plasma. Although plasma concentrations of cholesterol and nonesterified fatty acids changed during the periparturient period, their concentrations were not affected in CSF. In contrast, CSF Gln concentration tended to increase until calving, whereas CSF concentrations of BHBA, α-aminobutyric acid, Cit, Gly, Ile, Val, and Leu were increased in early lactation compared with the preparturient period. Because Gln is known to serve as neuronal substrate generating ATP, Gln is suggested to act as a central anorexigenic signal shortly before parturition. Moreover, due to their known anorexic effect, BHBA and Leu may potentially act as central signals and thereby suppress a sufficient increase in FI during early lactation.

Adiponectin and resistin in human cerebrospinal fluid and expression of adiponectin receptors in the human hypothalamus.

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/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. 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.