► Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5). ► Plasma irisin levels are higher in obese compared to anorexia nervosa. ► Irisin correlates with body mass index, fat mass ...and fat free mass. ► Circulating irisin correlates with insulin but not ghrelin. ► Physiological function of irisin may be improvement of glucose tolerance.
Irisin was recently identified as cleavage product of fibronectin type III domain containing 5 (FNDC5) and shown to increase energy expenditure in mice and humans and therefore was discussed as potential treatment option in obesity. However, the regulation of irisin under conditions of severely altered body weight such as anorexia nervosa and obesity remains to be investigated. We analyzed circulating irisin levels over a broad spectrum of body weight in 40 patients with anorexia nervosa (mean body mass index, BMI 12.6±0.7kg/m2), normal weight controls (22.6±0.9kg/m2) and obese patients with BMI of 30–40 (36.9±1.2kg/m2), 40–50 (44.9±1.1kg/m2) and >50 (70.1±2.7kg/m2, n=8/group). Correlation analyses were performed between irisin and different body indices, parameters of body composition and hormones involved in various homeostatic processes. Obese patients showed higher circulating irisin levels compared to normal weight and anorexic patients (p<0.05) resulting in a correlation of irisin with body weight (r=0.47, p<0.01) and BMI (r=0.50, p<0.001). Plasma irisin was also positively correlated with fat mass (r=0.48, p<0.01), body cell mass (r=0.45, p<0.01) and fat free mass (r=0.40, p<0.05). Insulin levels were positively correlated with irisin (r=0.45, p<0.01), whereas circulating ghrelin, cortisol, thyroid-stimulating hormone or C-reactive protein were not (p>0.05). These data indicate that circulating irisin is affected under conditions of altered BMI with highest levels in severely obese patients. The increase of irisin under conditions of obesity may indicate a physiological function to improve glucose tolerance which is often impaired in obese subjects.
Abstract Objective Deliberate self-harm behavior—without suicidal intent—is a serious health problem and may be studied as a clinical phenomenon in its own right. Empirical studies of ...sociodemographic and psychological correlates and risk factors are systematically reviewed. Methods We searched Medline, PsycINFO, PSYNDEX (German psychological literature), and reference lists. We targeted self-induced bodily harm without conscious suicidal intent. Studies on suicidal behavior or self-poisoning were only included if they also assessed nonsuicidal self-harm. Results Fifty-nine original studies met the criteria. Deliberate self-harm may occur at all ages, yet adolescents and young adults are at a higher risk. Evidence on gender is complex. Only 5 studies realize a prospective design (6 months to 10 years) and test predictors. The majority use cross-sectional and retrospective methods. No longitudinal study (separately) examines new incidence. Evidence of correlates encompasses distal/proximal, person/environment, and state/trait factors. Many studies report associations between current self-harm behavior and a history of childhood sexual abuse. Adolescent and adult self-harmers experience more frequent and more negative emotions, such as anxiety, depression, and aggressiveness, than persons who do not self-harm. Two studies yield specific interactions between childhood trauma and current traits and states such as low emotional expressivity, low self-esteem, and dissociation with respect to a vulnerability to self-harm. Conclusion Evidence of distal, biographical stressors is fairly strong. Proximal stressors have rarely been investigated; protective factors, hardly at all. Despite many findings of correlates, the data do not yet justify terming them risk factors . Longitudinal studies are needed.
The neural systems regulating food intake in obese individuals remain poorly understood. Previous studies applied positron emission tomography and manipulated hunger and satiety to investigate ...differences in appetitive processing between obese and normal-weight individuals. However, it is not known whether manipulation of stimulus value may yield different neural activity in obese as compared to control subjects when intrinsic physiological states are kept constant. We used functional magnetic resonance imaging to investigate 13 obese and 13 normal-weight subjects and manipulated food motivation by presenting visual food stimuli differing in their caloric content and energy density.
In contrast to controls, obese women selectively activated the dorsal striatum while viewing high-caloric foods. Moreover, in the high-calorie condition body mass index (BMI) predicted activation in the dorsal striatum, anterior insula, claustrum, posterior cingulate, postcentral and lateral orbitofrontal cortex.
The results indicate that in obese individuals simple visual stimulation with food stimuli activates regions related to reward anticipation and habit learning (dorsal striatum). Additionally, high-calorie food images yielded BMI-dependent activations in regions associated with taste information processing (anterior insula and lateral orbitofrontal cortex), motivation (orbitofrontal cortex), emotion as well as memory functions (posterior cingulate).
Collectively, the results suggest that the observed activation is independent of the physiological states of hunger and satiation, and thus may contribute to pathological overeating and obesity. Some of the observed activations (dorsal striatum, orbitofrontal cortex) are likely to be dopamine-mediated.
Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the ...regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague–Dawley rats were used and peripheral as well as brain tissue was processed for 125I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of 125I-nesfatin-1 with non-labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (−32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of 125I-nesfatin-1 bound to the receptor (EC50) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong 125I-nesfatin-1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions.
•Although our knowledge on nesfatin-1 is increasing, the receptor is still unknown.•125I-nesfatin-1 autoradiography was detected in (a.o.) the stomach and pancreas.•Central signals were observed in the hypothalamic paraventricular and dorsal motor nucleus.•Distribution data support the notion of nesfatin-1 being a pleiotropic hormone.
NUCB2/nesfatin-1 is an anorexigenic hormone with elevated levels in obese and decreased levels in anorexia nervosa (AN) patients. Moreover, a role in the regulation of stress and emotions was ...suggested by several rodent and preliminary human studies. Since anxiety and depression are common comorbidities in AN, we investigated the association of NUCB2/nesfatin-1 with anxiety, depression and perceived stress in AN.
We analyzed circulating NUCB2/nesfatin-1 levels in 64 female inpatients diagnosed with anorexia nervosa (body mass index, BMI; mean±SD, 14.7±2.3 kg/m2). At the same time anxiety (GAD-7), depression (PHQ-9), stress (PSQ-20) and disordered eating (EDI-2) were measured psychometrically.
No correlation was observed between NUCB2/nesfatin-1 and BMI (r = 0.06, p = 0.70). The study population was divided in patients with low anxiety (n = 32, GAD-7 scores, mean±SD, 7.5±3.3) and high anxiety (n = 32, 16.0±3.0, p<0.001). Patients with high anxiety scores displayed 65% higher NUCB2/nesfatin-1 levels (p = 0.04). This was reflected by a positive correlation of GAD-7 and NUCB2/nesfatin-1-levels (r = 0.32, p = 0.04). Scores of PSQ-20 (73.3±14.3 vs. 48.6±17.2) and PHQ-9 (18.8±5.0 vs. 10.3±5.1) were higher in the high anxiety group (p<0.001) but did not correlate with NUCB2/nesfatin-1 (p>0.05). EDI-2 total score was also higher in the high anxiety group (52.3±14.1 vs. 40.2±16.0, p = 0.02), while no correlations of EDI-2-scores with plasma NUCB2/nesfatin-1 were observed (p>0.05).
Circulating NUCB2/nesfatin-1 levels correlated positively with perceived anxiety, whereas no association with BMI or eating disorder symptoms was observed. NUCB2/nesfatin-1 might be primarily involved in the modulation of anxiety and subsequently in the regulation of eating habits and body weight in AN.
Highlights • NUCB2/nesfatin-1 is involved in the regulation of mood and stress. • NUCB2/nesfatin-1 is differentially implicated in the regulation of anxiety in men and women. • Sex-specific ...regulation of NUCB2/nesfatin-1 was also shown for perceived stress and depressiveness.
Using a standardized instrument to evaluate patients' stress reactions has become more important in daily clinical routines. Different signs or symptoms of stress are often unilaterally explored: the ...physiological, psychological or social aspects of stress disorders are each viewed on a single dimension. However, all dimensions afflict patients who have persistent health problems due to chronic stress. Therefore, it is important to use a multidimensional approach to acquire data. The 'Psycho-Physiological-Stress-Test' (PPST) was established to achieve a comprehensive understanding of stress and was further developed at the Charité-Universitätsmedizin Berlin in collaboration with the Psychological Department of Freie Universität Berlin. The PPST includes a series of varying stress phases, embedded in two periods of rest. Physiological and psychological parameters are simultaneously measured throughout the test session. Specifically, the PPST activates the sympathetic stress axis, which is measured by heart rate, blood pressure, respiration depth and rate, electro dermal activation and muscle tension (frontalis, masseter, trapezius). Psychological data are simultaneously collected, and include performance, motivation, emotion and behavior. After conducting this diagnostic test, it is possible to identify individual stress patterns that can be discussed with the individual patient to develop and recommend (outpatient) treatment strategies. This paper introduces the PPST as a standardized way to evaluate stress reactions by presenting the results from a sample of psychosomatic inpatients (n = 139) who were treated in Charité-Universitätsmedizin Berlin, Germany. We observed that the varying testing conditions provoked adjusted changes in the different physiological parameters and psychological levels.
•Phoenixin is a recently discovered peptide initially implicated in reproduction.•Phoenixin was also shown to have an anxiolytic effect in mice.•Phoenixin is detectable in the circulation in ...humans.•Phoenixin shows a negative association with anxiety in obese men.•Phoenixin might be an interesting target in the treatment of anxiety disorders.
Phoenixin was recently identified in the rat hypothalamus and initially implicated in reproductive functions. A subsequent study described an anxiolytic effect of the peptide. The aim of the study was to investigate a possible association of circulating phoenixin with anxiety in humans. We therefore enrolled 68 inpatients with a broad spectrum of psychometrically measured anxiety (GAD-7). We investigated men since a menstrual cycle dependency of phoenixin has been assumed. Obese subjects were enrolled since they often report psychological comorbidities. In addition, we also assessed depressiveness (PHQ-9) and perceived stress (PSQ-20). Plasma phoenixin levels were measured using a commercial ELISA. First, we validated the ELISA kit performing a spike-and-recovery experiment showing a variance of 6.7±8.8% compared to the expected concentrations over the whole range of concentrations assessed, while a lower variation of 1.6±0.8% was observed in the linear range of the assay (0.07–2.1ng/ml). We detected phoenixin in the circulation of obese men at levels of 0.68±0.50ng/ml. These levels showed a negative association with anxiety scores (r=−0.259, p=0.043), while no additional associations with other psychometric parameters were observed. In summary, phoenixin is present in the human circulation and negatively associated with anxiety in obese men, a population often to report comorbid anxiety.
Preeclampsia (PE) is a pregnancy-specific disorder characterized by sudden onset of hypertension and proteinuria in the second half of pregnancy (>20 wk). PE is strongly associated with abnormal ...placentation and an excessive maternal inflammatory response. Galectin-1 (Gal-1), a member of a family of carbohydrate-binding proteins, has been shown to modulate several processes associated with placentation and to promote maternal tolerance toward fetal antigens. Here, we show that Gal-1 exhibits proangiogenic functions during early stages of pregnancy, promoting decidual vascular expansion through VEGF receptor 2 signaling. Blocking Gal-1–mediated angiogenesis or lectin, galactoside-binding, soluble, 1 deficiency results in a spontaneous PE-like syndrome in mice, mainly by deregulating processes associated with good placentation and maternal spiral artery remodeling. Consistent with these findings, we observed a down-regulation of Gal-1 in patients suffering from early onset PE. Collectively, these results strengthen the notion that Gal-1 is required for healthy gestation and highlight Gal-1 as a valuable biomarker for early PE diagnosis.
Abstract Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. ...The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells.
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