Anne Ahnis

The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index

Ghrelin is the only known peripherally produced and centrally acting peptide hormone stimulating food intake. The acylation of ghrelin is essential for binding to its receptor. Recently, the ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) was identified in mice, rats and humans. In addition to gastric mucosal expression, GOAT was also detected in the circulation of rodents and its expression was dependent on metabolic status. We investigated whether GOAT is also present in human plasma and whether expression levels are affected under different conditions of body weight. Normal weight, anorexic and obese subjects with body mass index (BMI) 30-40, 40-50 and >50 were recruited (n=9/group). In overnight fasted subjects GOAT protein expression was assessed by Western blot and ghrelin measured by ELISA. GOAT protein was detectable in human plasma. Anorexic patients showed reduced GOAT protein levels (-42%, p<0.01) whereas obese patients with BMI>50 had increased concentrations (+34%) compared to normal weight controls. Ghrelin levels were higher in anorexic patients compared to all other groups (+62-78%, p<0.001). Plasma GOAT protein expression showed a positive correlation with BMI (r=0.71, p<0.001) and a negative correlation with ghrelin (r=-0.60, p<0.001). Summarized, GOAT is also present in human plasma and GOAT protein levels depend on the metabolic environment with decreased levels in anorexic and increased levels in morbidly obese patients. These data may indicate that GOAT counteracts the adaptive changes of ghrelin observed under these conditions and ultimately contributes to the development or maintenance of anorexia and obesity as it is the only enzyme acylating ghrelin.

Irisin Levels are Not Affected by Physical Activity in Patients with Anorexia Nervosa

Irisin was recently identified as muscle-derived hormone that increases energy expenditure. Studies in normal weight and obese subjects reported an increased irisin expression following physical activity, although inconsistent results were observed. Increased physical activity in a subgroup of patients with anorexia nervosa (AN) complicates the course of the disease. Since irisin could account for differences in clinical outcomes, we investigated irisin levels in anorexic patients with high and moderate physical activity to evaluate whether irisin differs with increasing physical activity. Hospitalized female anorexic patients (n = 39) were included. Plasma irisin measured by enzyme-linked immunosorbent assay and locomotor activity were assessed at the same time. Patients were separated into two groups (n = 19/group; median excluded): moderate and high activity (6331 ± 423 vs. 13743 ± 1047 steps/day, p < 0.001). The groups did not differ in body mass index (14.2 ± 0.4 vs. 15.0 ± 0.4 kg/m2), irisin levels (558.2 ± 26.1 vs. 524.9 ± 25.2 ng/ml), and body weight-adjusted resting energy expenditure (17.6 ± 0.3 vs. 18.0 ± 0.3 kcal/kg/day, p > 0.05), whereas body weight-adjusted total energy expenditure (46.0 ± 1.4 vs. 41.1 ± 1.1 kcal/kg/day), metabolic equivalents (METs, 1.9 ± 0.1 vs. 1.7 ± 0.1 METs/day), body weight-adjusted exercise activity thermogenesis (1.8 ± 0.5 vs. 0.6 ± 0.3 kcal/kg/day), duration of exercise (18.6 ± 4.7 vs. 6.2 ± 3.1 min/day), and body weight-adjusted non-exercise activity thermogenesis (21.6 ± 1.0 vs. 18.8 ± 0.8 kcal/kg/day) were higher in the high activity compared to the moderate activity group (p < 0.05). No correlations were observed between irisin and activity parameters in the whole sample (p > 0.05). In conclusion, the current data do not support the concept of irisin being induced by exercise, at least not under conditions of severely reduced body weight like AN.

Sex-specific regulation of NUCB2/nesfatin-1: Differential implication in anxiety in obese men and women

Nesfatin-1 is cleaved from nucleobindin2 (NUCB2) and implicated in the regulation of hunger and satiety as anorexigenic peptide hormone. Circulating NUCB2/nesfatin-1 is elevated in obesity and decreased in anorexia nervosa. In addition, a role in the regulation of stress, anxiety and depression has been demonstrated. First evidence suggested that NUCB2/nesfatin-1 might be regulated in a sex-specific manner. Thus, we investigated NUCB2/nesfatin-1 plasma levels in association with perceived stress, anxiety and depressiveness in obese men and women. We enrolled 140 inpatients (87 female, 53 male; body mass index, BMI, 30.3-81.7 kg/m(2)) hospitalized due to obesity with mental and somatic comorbidities. Perceived stress (PSQ-20), anxiety (GAD-7), and depressiveness (PHQ-9) were measured psychometrically, and at the same time NUCB2/nesfatin-1 plasma levels by ELISA. Males and females did not differ in terms of age and BMI. NUCB2/nesfatin-1 did not show a correlation with age or BMI. Mean NUCB2/nesfatin-1 levels (+25%, p<0.001) as well as mean scores for perceived stress (+26%, p < 0.01), anxiety (+54%, p < 0.001) and depressiveness (+32%, p = 0.02) were higher in females compared to males. Scores for perceived stress (r = 0.39; p < 0.001) and depressiveness (r = 0.35; p < 0.01) showed a positive correlation with NUCB2/nesfatin-1 in women, while in men no correlation was observed (p>0.19). The strongest association was observed between NUCB2/nesfatin-1 and anxiety with a positive correlation in women (r = 0.54; p < 0.001), while in men even an inverse correlation was found (r = -0.32; p = 0.03). This result was reflected in higher NUCB2/nesfatin-1 levels in women with high versus low anxiety (+51%, p<0.001) and an opposite alteration in men (-17%, p = 0.04) after a median split into two groups with high and low anxiety. In conclusion, circulating NUCB2/nesfatin-1 showed a positive correlation with anxiety, perceived stress, and depressiveness in obese women. In men, no correlation with perceived stress and depressiveness was observed, whereas the association with anxiety was inverse, pointing towards a sex-specific regulation. These results corroborate the suggestion of NUCB2/nesfatin-1 being relevantly involved in the regulation of mood and stress in a sex-specific way.

NUCB2/nesfatin-1 Is Associated with Elevated Levels of Anxiety in Anorexia Nervosa

Objective 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. Methods 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. Results 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). Conclusions 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.

Plasma bile acids show a positive correlation with body mass index and are negatively associated with cognitive restraint of eating in obese patients

Bile acids may be involved in the regulation of food intake and energy metabolism. The aim of the study was to investigate the association of plasma bile acids with body mass index (BMI) and the possible involvement of circulating bile acids in the modulation of physical activity and eating behavior. Blood was obtained in a group of hospitalized patients with normal weight (BMI 18.5–25 kg/m2), underweight (anorexia nervosa, BMI < 17.5 kg/m2) and overweight (obesity with BMI 30–40, 40–50 and >50 kg/m2, n = 14–15/group) and plasma bile acid concentrations assessed. Physical activity and plasma bile acids were measured in a group of patients with anorexia nervosa (BMI 14.6 ± 0.3 kg/m2, n = 43). Lastly, in a population of obese patients (BMI 48.5 ± 0.9 kg/m2, n = 85), psychometric parameters related to disordered eating and plasma bile acids were assessed. Plasma bile acids showed a positive correlation with BMI (r = 0.26, p = 0.03) in the population of patients with broad range of BMI (9–85 kg/m2, n = 74). No associations were observed between plasma bile acids and different parameters of physical activity in anorexic patients (p > 0.05). Plasma bile acids were negatively correlated with cognitive restraint of eating (r = −0.30, p = 0.008), while no associations were observed with other psychometric eating behavior-related parameters (p > 0.05) in obese patients. In conclusion, these data may point toward a role of bile acids in the regulation of body weight. Since plasma bile acids are negatively correlated with the cognitive restraint of eating in obese patients, this may represent a compensatory adaptation to prevent further overeating.

Psychological and sociodemographic predictors of premature discontinuation of a 1-year multimodal outpatient weight-reduction program: an attrition analysis

Objective Attrition rates of up to 77% have been reported in conservative weight-reduction programs for the treatment of obesity. In view of the cost of such programs to the health system, there is a need to identify the variables that predict premature discontinuation of treatment. Previous studies have focused mainly on somatic and sociodemographic parameters. The prospective influence of psychological factors has not been systematically investigated to date. Methods A total of 164 patients (138 of whom were women) with a mean age of 45 years and a mean body mass index of 39.57 participated in a 1-year outpatient weight-reduction program at the Charité – Universitätsmedizin Berlin University Hospital. The program included movement therapy, dietary advice, psychoeducational and behavioral interventions, relaxation procedures, and consultations with a specialist in internal medicine and a psychologist. Patients also underwent regular laboratory and psychological testing. The results were evaluated using a t-test, χ2-test, and logistic regression analysis. Results Seventy-one of the 164 patients (61 women, mean age = 43 years, mean body mass index = 39.53) withdrew before the end of the program (attrition rate = 43.3%). While there were no differences between the somatic and metabolic characteristics of those who withdrew and those who remained, the sociodemographic and psychological factors had some relevance. In particular, “expectation of self-efficacy” (Fragebogen zu Selbstwirksamkeit, Optimismus und Pessimismus [SWOP]), “not working,” “tiredness” (Berliner Stimmungsfragebogen [BSF]), “pessimism” (SWOP) and “positive reframing” (Brief-COPE) were found to play a role in whether participants subsequently dropped out of the treatment. “Support coping” (Brief-COPE) and “older age” prior to the start of treatment were identified as variables that promoted treatment adherence. Conclusion The results are discussed in light of previous findings and with regard to whether the modules of the weight-reduction program should be adapted.

Phoenixin is negatively associated with anxiety in obese men

HighlightsPhoenixin 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. Abstract 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 (0.07–2.1 ng/ml). We detected phoenixin in the circulation of obese men at levels of 0.68 ± 0.50 ng/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.

Surgically and Conservatively Treated Obese Patients Differ in Psychological Factors, Regardless of Body Mass Index or Obesity- Related Co-Morbidities: A Comparison between Groups and an Analysis of Predictors

Objective For the treatment of obesity, both conservative and surgical procedures are available. Psychological factors are likely to influence the choice of treatment; however, to date, systematic studies that investigate these factors are few in number. The aim of our study was to analyze whether patients who undergo a surgical treatment differ from those who require a conservative treatment in regard to psychological factors, regardless of their somatic conditions. Furthermore, predictors of treatment choice will be examined. Methods A total of 244 patients (189 women), with a mean body mass index of 45.1 kg/m2, underwent a weight reduction treatment, with 126 patients undergoing bariatric surgery and 118 patients participating in a conservative, multimodal outpatient weight reduction program. Differences in the results of the psychological questionnaires between conservatively and surgically treated patients were evaluated through the use of t-tests, χ2-tests and an ANCOVA. For the analysis of the predictors, logistic regression models were calculated. Results Surgically and conservatively treated obese patients differ in psychological, somatic, and socio-demographic factors. The psychological differences between the groups are independent of obesity-related co-morbidities, such as body mass index (BMI), type 2 diabetes mellitus, hypertension and coronary heart disease. The following psychological and somatic factors equally predict the choice of bariatric surgery: apathy, delegated active coping, a sense of coherence, complaints, type 2 diabetes mellitus, BMI, and age. Conclusion Longitudinal studies are required to assess the predictive value of the psychological factors in regard to the postsurgical weight course to improve the pre-surgical screening and treatment selection process. The pre-surgical identification of psychological predictors should result in a more personalized medicine course and may ensure long term outcomes.

Alterations of circulating NUCB2/nesfatin-1 during short term therapeutic improvement of anxiety in obese inpatients

In addition to its anorexigenic properties in the neuroendocrine regulation of hunger and satiety, mounting evidence indicates a role for NUCB2/nesfatin-1 in the regulation of emotional stress responses which seems to occur in a sex-specific way. In the present study, we investigated the association of NUCB2/nesfatin-1 plasma levels with anxiety, depressiveness and perceived stress in obese men and women and their alterations during inpatient treatment. We expected a decrease of NUCB2/nesfatin-1 levels in female and an increase in male patients reporting a relevant alleviation of anxiety. We analyzed 69 inpatients (44 female, 25 male; body mass index, mean: 50.2±9.5kg/m2, range: 31.8-76.5kg/m2; mean age: 45.0±12.4years) hospitalized due to morbid obesity with mental (not necessarily anxiety disorders) and somatic comorbidities. NUCB2/nesfatin-1 plasma levels were measured by ELISA. Anxiety (GAD-7), depressiveness (PHQ-9) and perceived stress (PSQ-20) were concurrently determined as patient-reported outcomes. All measurements were carried out at the initiation of and during inpatient treatment when a clinically meaningful improvement of anxiety was achieved (≥5 points on GAD-7) or missed (±1 point). NUCB2/nesfatin-1 was positively correlated with anxiety scores in women at the beginning of (r=0.411; p=0.006) and during (r=0.301; p=0.047) inpatient treatment. In men, a significant negative correlation was observed following treatment (r=-0.469; p=0.018), while at the outset of treatment only a trend was observed (r=-0.381; p=0.059). Unexpectedly, neither women (n=19; at beginning vs. during treatment; 0.49±1.00ng/ml vs. 0.38±0.72ng/ml; p=0.687) nor men (n=9; 0.17±0.31ng/ml vs. 0.19±0.36ng/ml; p=0.427) who improved in anxiety scores (p<0.001) displayed significant changes of NUCB2/nesfatin-1 plasma levels, although the direction of change was as expected with a decrease in women (-23.3%) and an increase in men (+12.4%). In addition, the change of NUCB2/nesfatin-1 was not explained by the course of anxiety (women: p=0.587; men: p=0.373). In conclusion, women and men showed an inverse association between NUCB2/nesfatin-1 and anxiety with a positive correlation in women and a negative correlation in men (although this correlation was not statistically significant in men at the beginning of treatment). However, no significant change of NUCB2/nesfatin-1 following improvement of anxiety has been observed. This might be due to the short observation interval, or due to too small anxiety improvements associated with too low baseline anxiety levels.

Changes in self-reported eating patterns after laparoscopic sleeve gastrectomy: a pre-post analysis and comparison with conservatively treated patients with obesity.

BACKGROUND Patients with severe obesity need to adapt to surgically induced changes in their eating behaviors to maintain treatment success. OBJECTIVES This study examined the effects of laparoscopic sleeve gastrectomy (LSG) on weight loss and on 3 dimensions of eating behavior, namely, cognitive restraint, disinhibition, and hunger. Outcomes of the LSG group were compared with a group of conservatively treated (CT) patients, who underwent a 1-year multimodal weight-reduction group program that included dietary advice, physical exercise, psychoeducation, cognitive-behavioral therapy, training in Jacobsons progressive muscle relaxation, and social group support. SETTING The study setting was a multidisciplinary obesity center located in a university hospital. METHODS A sample of 102 patients with obesity were investigated using the Three-Factor Eating Questionnaire before and, on average, 19 (±5) months after weight loss intervention. Of the 102 patients, 62 (age 45.8±10.8 years, 71% females) underwent LSG, and 40 patients (age 50.6±11.3 years, 77.5% females) underwent the CT program. Patients were assigned to either the surgical or the nonsurgical intervention group following clinical guidelines and patient preference. RESULTS In the LSG group, total weight loss was 25.9±11.0%, excess weight loss was 52.8±24.1%, and body mass index decreased from 51.4±8.1 to 38.0±7.8 kg/m². In the CT group, total weight loss was 5.4±10.6%, excess weight loss was 13.9±27.1%, and body mass index decreased from 40.3±6.7 to 38.0±7.2 kg/m². Significant improvements in self-reported eating behaviors were observed in both groups, that is, an increased cognitive restraint of eating, a decreased disinhibition of eating control, and a reduced degree of perceived hunger. In contrast, whereas Three-Factor Eating Questionnaire scores before weight loss intervention did not differ between groups, LSG patients reported significantly greater reductions in disinhibition and hunger than CT patients did after weight loss intervention. In both groups, greater weight loss was associated with decreased hunger sensations. CONCLUSION In the second follow-up year, LSG was associated with greater weight loss and greater improvements in self-reported eating behaviors compared with conservative treatment.