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This study evaluated the impact of obesity on abdominal ultrasound diagnostics and assessed effect of high-performance ultrasound probes increased imaging quality. Lean and obese subjects (n = 40; 58% female) were categorized according to body mass index (BMI, 21 to 48 kg/m 2 ). A highly standardized ultrasound examination of the abdomen was performed by trained examiners using three different probes in randomized order (standard probe versus two high-performance probes). Quality of B-mode and duplex ultrasound were assessed using a custom scoring approach for depiction of liver and kidney anatomy and vascularization. Across probes, imaging quality of hepatic and kidney anatomy was inversely related with BMI (P < 0.03, r < - 0.35). Age, sex, and BMI explained 51% of the variance within the ultrasound quality score, with β = - 0.35, P < 0.0001 for BMI. Compared to the standard probe, high-performance probes allowed for a better depiction of kidney and liver anatomy in subjects above BMI 35 kg/m 2 (n = 20, all P < 0.05), resulting in a less pronounced deterioration of imaging quality with increased BMI (all P < 0.05). In conclusion the study shows that obesity impairs ultrasound imaging quality of abdominal anatomy. The application of high-performance probes can increase anatomic depiction in obese patients.Registration number of the German Registry of Clinical Studies: DRKS00023498., (© 2023. The Author(s).)

Background: The refeeding syndrome (RFS) is an oftentimes-unrecognized complication of reintroducing nutrition in malnourished patients that can lead to fatal cardiovascular failure. We hypothesized that a clinical decision support system (CDSS) can improve RFS recognition and management., Methods: We developed an algorithm from current diagnostic criteria for RFS detection, tested the algorithm on a retrospective dataset and combined the final algorithm with therapy and referral recommendations in a knowledge-based CDSS. The CDSS integration into clinical practice was prospectively investigated for six months., Results: The utilization of the RFS-CDSS lead to RFS diagnosis in 13 out of 21 detected cases (62%). It improved patient-related care and documentation, e.g., RFS-specific coding (E87.7), increased from once coded in 30 month in the retrospective cohort to four times in six months in the prospective cohort and doubled the rate of nutrition referrals in true positive patients (retrospective referrals in true positive patients 33% vs. prospective referrals in true positive patients 71%)., Conclusion: CDSS-facilitated RFS diagnosis is possible and improves RFS recognition. This effect and its impact on patient-related outcomes needs to be further investigated in a large randomized-controlled trial.

Context: Research in lipodystrophy (LD) and its treatment with metreleptin has not only helped patients with LD but has opened new directions in investigating leptin's role in metabolism and the regulation of eating behavior. Previously, in a study with patients with LD undergoing metreleptin treatment using functional magnetic resonance imaging (MRI), we found significantly increased resting-state brain connectivity in 3 brain areas including the hypothalamus., Objective: In this study, we aimed to reproduce our functional MRI findings in an independent sample and compare results to healthy participants., Design: Measurements in 4 female patients with LD undergoing metreleptin treatment and 3 healthy untreated controls were performed at 4 different time points over 12 weeks. To identify treatment-related brain connectivity alterations, eigenvector centrality was computed from resting-state functional MRI data for each patient and each session. Thereafter, analysis aimed at detecting consistent brain connectivity changes over time across all patients., Results: In parallel to metreleptin treatment of the patients with LD, we found a significant brain connectivity increase in the hypothalamus and bilaterally in posterior cingulate gyrus. Using a 3-factorial model, a significant interaction between group and time was found in the hypothalamus., Conclusions: Investigating brain connectivity alterations with metreleptin treatment using an independent sample of patients with LD, we have reproduced an increase of brain connectivity in hedonic and homeostatic central nervous networks observed previously with metreleptin treatment. These results are an important contribution to ascertain brain leptin action and help build a foundation for further research of central nervous effects of this important metabolic hormone., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Behaviorally, the most pronounced effects of leptin substitution in leptin deficiency are the hunger-decreasing and postprandial satiety-prolonging effects of the adipokine. Previously, with functional magnetic resonance imaging (MRI), we and others showed that eating behavior-controlling effects are at least in part conveyed by the reward system. However, to date, it is unclear if leptin only modulates eating behavior specific brain reward action or if it also alters the reward function of the brain unrelated to eating behavior., Objective: We investigated with functional MRI the effects of metreleptin on the reward system in a reward task unrelated to eating behavior, the monetary incentive delay task., Design: Measurements in 4 patients with the very rare disease of lipodystrophy (LD), resulting in leptin deficiency, and 3 untreated healthy control persons were performed at 4 different time points: before start and over 12 weeks of metreleptin treatment. Inside the MRI scanner, participants performed the monetary incentive delay task and brain activity during the reward receipt phase of the trial was analyzed., Results: We found a reward-related brain activity decrease in our 4 patients with LD over the 12 weeks of metreleptin treatment in the subgenual region, a brain area associated with the reward network, which was not observed in our 3 untreated healthy control persons., Conclusions: These results suggest that leptin replacement in LD induces changes of brain activity during reward reception processing completely unrelated to eating behavior or food stimuli. This could suggest eating behavior-unrelated functions of leptin in the human reward system., Trial Registration: The trial is registered as trial No. 147/10-ek at the ethics committee of the University of Leipzig and at the State Directorate of Saxony (Landesdirektion Sachsen)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Behavioural weight loss (BWL) treatment is the standard evidence-based treatment for severe obesity (SO; body mass index ≥40.0 kg/m 2 or ≥35.0 kg/m 2 with obesity-related comorbidity), leading to moderate weight loss which often cannot be maintained in the long term. Because weight loss depends on patients' use of weight management skills, it is important to support them in daily life. In an ecological momentary intervention design, this clinical trial aims to adapt, refine and evaluate a personalised cognitive-behavioural smartphone application (app) in BWL treatment to foster patients' weight management skills use in everyday life. It is hypothesised that using the app is feasible and acceptable, improves weight loss and increases skills use and well-being., Methods and Analysis: In the pilot phase, the app will be adapted, piloted and optimised for BWL treatment following a participatory patient-oriented approach. In the subsequent single-centre, assessor-blind, exploratory randomised controlled trial, 90 adults with SO will be randomised to BWL treatment over 6 months with versus without adjunctive app. Primary outcome is the amount of weight loss (kg) at post-treatment (6 months), compared with pretreatment, derived from measured body weight. Secondary outcomes encompass feasibility, acceptance, weight management skills use, well-being and anthropometrics assessed at pretreatment, midtreatment (3 months), post-treatment (6 months) and 6-month follow-up (12 months). An intent-to-treat linear model with randomisation arm, pretreatment weight and stratification variables as covariates will serve to compare arms regarding weight at post-treatment. Secondary analyses will include linear mixed models, generalised linear models and regression and mediation analyses. For safety analysis (serious) adverse events will be analysed descriptively., Ethics and Dissemination: The study was approved by the Ethics Committee of the University of Leipzig (DE-21-00013674) and notified to the Federal Institute for Drugs and Medical Devices. Study results will be disseminated through peer-reviewed publications., Registration: This study was registered at the German Clinical Trials Register (DRKS00026018), www.drks.de., Trial Registration Number: DRKS00026018., Competing Interests: Competing interests: Professor Hilbert received: research grants on obesity and eating disorders from the German Federal Ministry of Education and Research, German Research Foundation, and Roland Ernst Foundation for Healthcare; royalties for books on the treatment of obesity and eating disorders with Hogrefe; honoraria for workshops and lectures on obesity and eating disorders and their treatment; honoraria as editor of the International Journal of Eating Disorders and the journal Psychotherapeut; honoraria as a reviewer from Mercator Research Centre Ruhr, Oxford University Press and the German Society for Nutrition; and honoraria as a consultant for WeightWatchers, Zweites Deutsches Fernsehen and Takeda., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Refeeding syndrome (RFS) can occur in malnourished patients when normal, enteral, or parenteral feeding is resumed. The syndrome often goes unrecognized and may, in the most severe cases, result in death. The diagnosis of RFS can be crucially facilitated by the use of clinical decision support systems (CDSS)., Methods: The literature in PubMed was searched for current treatment recommendations, randomized intervention studies, and publications on RFS and CDSS. We also took account of insights gained from the development and implementation of our own CDSS for the diagnosis of RFS., Results: The identification of high-risk patients and the recognition of manifest RFS is clinically challenging due to the syndrome's unspecific symptoms and physicians' lack of awareness of the risk of this condition. The literature shows that compared to patients without RFS, malnourished patients with RFS have significantly greater 6-month mortality (odds ratio 1.54, 95% confidence interval: [1.04; 2.28]) and an elevated risk of admission to intensive care (odds ratio 2.71 [1.01; 7.27]). In a prospective testing program, use of our own CDSS led to correct diagnosis in two thirds of cases., Conclusion: RFS is difficult to detect and represents a high risk to the patients affected. Appropriate CDSS can identify such patients and ensure proper professional care.

Introduction: The decision for obesity surgery (OS) is complex and strongly driven by patients' preference. This study aimed to examine patients' preference for OS before and after behavioral weight loss treatment (BWLT), associated patient characteristics, its role in predicting the receipt of OS after BWLT, and potential mediators., Methods: Data of N = 431 adults with obesity starting a 1-year routine care obesity BWLT were analyzed. Patients were interviewed before (pre-BWLT) and after BWLT (post-BWLT) regarding their preference for OS, and anthropometric, medical, and psychological data were collected., Results: Only a minority of patients (11.6%) had an explicit preference for OS pre-BWLT. Post-BWLT, the number of patients preferring OS significantly increased (27.4%). Patients with a constant or emerging preference for OS showed less favorable anthropometric, psychological, and medical characteristics than patients without or with a vanishing preference for OS. Patients' pre-BWLT preference for OS significantly predicted receiving OS post-BWLT. This association was mediated by higher body mass index pre- and post-BWLT, but not by less percentage total body weight loss (%TBWL) through BWLT., Conclusion: Although the preference for OS pre-BWLT predicted the receipt of OS post-BWLT, it was not associated with %TBWL during BWLT. Further prospective studies with multiple assessment time points during BWLT may help understand when and why patients' attitude toward OS changes, and identify possible mediators on the association between the preference and receipt of OS., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Social cognition includes understanding the mental states (thoughts, feelings, intentions, desires, and beliefs) of others - so-called 'theory of mind' or 'mindreading'. Recent studies have shown an impact of age and sex. Here, we applied the 'Reading the Mind in the Eyes' Test (RMET) that measures the ability to identify mental states from the eye region of the face. RMET accuracy was measured and analyzed in a large population-based sample ( N  = 1603) across the whole adult age-range from 19 to 79 years with effect size analyses (Hedges' g ). Overall test performance was lower in older than younger women and men, whereas differences between women and men were almost negligible across the whole cohort. In a further analysis focusing on age-specific sex differences, RMET accuracy was higher for women below 45 years compared to men. This sex effect nearly vanished in older people above 45 years of age. Results were verified in a sub-cohort after excluding participants with neurological and psychiatric conditions, and with another cut-off, i.e. 50 years of age. In conclusion, results suggest that mindreading declines with age. Overall sex effects were small and results suggest that age-related hormonal and social factors may impact mental state perception. Future mega-analyses and longitudinal studies including hormonal and social measures are needed to validate the interaction between RMET performance, aging and sex., Competing Interests: The authors state that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Crown Copyright © 2022 Published by Elsevier Ltd.)

This narrative review aims to pinpoint mental and behavioral effects of starvation, which may be triggered by hypoleptinemia and as such may be amenable to treatment with leptin receptor agonists. The reduced leptin secretion results from the continuous loss of fat mass, thus initiating a graded triggering of diverse starvation related adaptive functions. In light of leptin receptors located in several peripheral tissues and many brain regions adaptations may extend beyond those of the hypothalamus-pituitary-end organ-axes. We focus on gastrointestinal tract and reward system as relevant examples of peripheral and central effects of leptin. Despite its association with extreme obesity, congenital leptin deficiency with its many parallels to a state of starvation allows the elucidation of mental symptoms amenable to treatment with exogenous leptin in both ob/ob mice and humans with this autosomal recessive disorder. For starvation induced behavioral changes with an intact leptin signaling we particularly focus on rodent models for which proof of concept has been provided for the causative role of hypoleptinemia. For humans, we highlight the major cognitive, emotional and behavioral findings of the Minnesota Starvation Experiment to contrast them with results obtained upon a lesser degree of caloric restriction. Evidence for hypoleptinemia induced mental changes also stems from findings obtained in lipodystrophies. In light of the recently reported beneficial cognitive, emotional and behavioral effects of metreleptin-administration in anorexia nervosa we discuss potential implications for the treatment of this eating disorder. We postulate that leptin has profound psychopharmacological effects in the state of starvation., Competing Interests: Conflict of interest statements Johannes Hebebrand, Gertraud Gradl-Dietsch, and Jochen Antel declare that they will be named as inventors in a patent application that the University of Duisburg-Essen prepares to file on the use of leptin analogues for the treatment of depression. Johannes Hebebrand and Jochen Antel declare that were named as inventors in a patent application that the University of Duisburg-Essen had filed on the use of leptin analogues for treating anorexia nervosa and related conditions. Johannes Hebebrand received speaker’s honoraria from Amryt Pharmaceuticals and from Novo-Nordisk. Haiko Schlögl has consulted for Aegerion Pharmaceuticals. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Lipodystrophy (LD) syndromes are rare heterogeneous disorders characterized by reduction or absence of subcutaneous fat, low or nondetectable leptin concentrations in blood and impaired hunger/satiety regulation. Metreleptin treatment reverses metabolic complications and improves eating behavior in LD. Because depression in anorexia nervosa (AN), which is also characterized by hypoleptinemia, improves substantially upon treatment with metreleptin, we hypothesized that metreleptin substitution may be associated with an antidepressant effect in patients with LD, too., Methods: In this ancillary study, 10 adult patients with LD were treated with metreleptin. To assess depressive symptoms, the self-rating questionnaire Beck's Depression Inventory (BDI) was filled in at preestablished time points prior (T1) and after initiation of metreleptin (T2: 1 week; T3: 4 weeks; T4: 12 weeks) dosing. The differences between time points were tested with nonparametric Friedman's analysis of variance. Sensitivity analyses were performed upon exclusion of the BDI items addressing appetite and weight changes., Results: According to their BDI scores, 4 patients had mild depression and 2 had moderate depression at baseline. Friedman's test revealed significant differences in BDI scores between the four time points. Post hoc analyses revealed that the difference between T1 and T3 was significant upon Bonferroni correction (p = 0.034, effect size r = 0.88). The sensitivity analyses upon exclusion of the appetite and weight change items again revealed a significant Friedman's test and significant Bonferroni corrected differences in the revised BDI scores between T1 versus T2 (p = 0.002, r = 0.99) and T1 versus T3 (p = 0.007, r = 0.79)., Discussion/conclusion: Our study for the first time revealed suggestive evidence for an antidepressant effect of metreleptin in patients with LD. Metreleptin caused a rapid drop in depression scores within 1 week of treatment. A reduction of the depression score was also observed in 2 of the 3 LD patients whose BDI scores were in the normal range before start of the treatment. The reduction in total scores of BDI was still apparent after 3 months (T4) of dosing. This observation matches findings obtained in clinical case studies of AN patients, in whom depression scores also dropped during the first week of metreleptin treatment. It needs to be noted that by the nature of this observational study without a placebo group, nonspecific treatment expectation affecting mood cannot fully be ruled out., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: The obesity treatment program " Leipziger Adipositasmanagement " is a long-term (i. e., four years long) conservative treatment program which is completely covered by a public health insurance company for patients with obesity grades 2 and 3 (i. e., body mass index > 35 kg/m 2 ). Here we evaluate the effectiveness of the first part of the program which was on average 72 weeks long., Methods: Body weight, body circumferences, metabolic and psychological parameters were collected prior to the start (t 0 ) and after completion of the first part (t 1 ). The whole first treatment part was completed by 243 persons. The analysis design was a prospective evaluation of clinical real world data., Results: Treatment costs per patient were 2,022 € on average. There were significant clinically meaningful improvements from t 0 to t 1 . On average, patients lost 5 kg (95 % confidence interval, KI 3.8 to 6.2 kg) or 4 % (KI 3.1 to 4.9 %) of their initial body weight. The hemoglobin A1c value decreased from 5.9 % to 5.6 % in all patients and from 6.7 % to 6.2 % in diabetic patients. Further metabolic (e. g., low density lipoprotein and total cholesterol) and psychological (e. g., quality of life) parameters improved significantly as well., Conclusions: The available real world data show, that an obesity treatment program, which is completely covered by a public health insurance company, can reach a clinically significant weight loss with metabolic improvements. The treatment program " Leipziger Adipositasmanagement " contributes to improving long-term treatment of obesity in Germany., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: Metreleptin treatment in lipodystrophy patients improves eating behavior with increased satiety and reduced hunger. However, no data are available whether effects are maintained beyond 52 weeks of treatment., Methods: A prospective study with measurements at baseline and at >150 weeks of metreleptin treatment was performed. Five female lipodystrophy patients with indication for metreleptin were included. Behavioral aspects of hunger- and satiety regulation were assessed by validated eating behavior questionnaires and visual analog scales assessing hunger and satiety feelings before and after a standardized meal., Results: Hunger rated on visual analog scales at 120 min after the meal significantly decreased from 46 ± 10 mm at baseline to 17 ± 6 mm at long-term assessment. Furthermore, satiety at 5 and 120 min after the meal significantly increased from baseline to long-term assessment (5 min: 70 ± 7 mm to 87 ± 3 mm; 120 min: 43 ± 10 mm to 79 ± 8 mm). On the Three Factor Eating Questionnaire, the mean value of factor 3 (hunger) significantly decreased from 9.2 ± 0.2 at baseline to 2.6 ± 1.5 at long-term assessment. In the Inventory of Eating Behavior and Weight Problems Questionnaire, mean values for scale 2 (strength and triggering of desire to eat) and scale 7 (cognitive restraint of eating) significantly decreased from baseline (31.6 ± 4.8 and 11.4 ± 2.2, respectively) to long-term assessment (14.0 ± 2.1 and 10.0 ± 1.9)., Conclusion: First evidence is presented that long-term metreleptin treatment of >150 weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Fetuin B is an adipokine/hepatokine which is significantly elevated in insulin resistance/type 2 diabetes mellitus and hepatic steatosis. Regulation of fetuin B in patients with lipodystrophy (LD) - a disease group which is characterized by subcutaneous adipose tissue loss, hypertriglyceridemia, hepatic steatosis, insulin resistance, and dysregulation of several adipokines - has not been elucidated so far., Material and Methods: Serum fetuin B levels were determined in 37 patients with LD, as well as in a control cohort consisting of 37 non-LD participants matched for age, gender, and body mass index. Furthermore, fetuin B was correlated with parameters of lipid metabolism, glucose control, renal function, and inflammation., Results: Median fetuin B serum levels were not significantly different between patients with LD (2980.7 µg/l; interquartile range: 841.7 µg/l) and non-LD controls (2647.3 µg/l; interquartile range: 923.6 µg/l; p = .105). Fetuin B was associated with age, body mass index, markers of renal function, and C reactive protein (CRP) in univariate correlation analyses. The associations with age and creatinine remained significant in multiple linear regression analysis., Conclusions: Fetuin B serum concentrations are not significantly different between patients with LD and non-LD controls. Fetuin B does not seem to be a major pathogenetic factor in LD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Brain-derived neurotrophic factor (BDNF), an important neural growth factor, has gained growing interest in neuroscience, but many influencing physiological and analytical aspects still remain unclear. In this study we assessed the impact of storage time at room temperature, repeated freeze/thaw cycles, and storage at -80 °C up to 6 months on serum and ethylenediaminetetraacetic acid (EDTA)-plasma BDNF. Furthermore, we assessed correlations of serum and plasma BDNF concentrations in two independent sets of samples. Coefficients of variations (CVs) for serum BDNF concentrations were significantly lower than CVs of plasma concentrations ( n = 245, p = 0.006). Mean serum and plasma concentrations at all analyzed time points remained within the acceptable change limit of the inter-assay precision as declared by the manufacturer. Serum and plasma BDNF concentrations correlated positively in both sets of samples and at all analyzed time points of the stability assessment ( r = 0.455 to r s = 0.596; p < 0.004). In summary, when considering the acceptable change limit, BDNF was stable in serum and in EDTA-plasma up to 6 months. Due to a higher reliability, we suggest favoring serum over EDTA-plasma for future experiments assessing peripheral BDNF concentrations., Competing Interests: The authors declare no conflict of interest.

Objective: Lipodystrophy (LD) syndromes are associated with diabetes mellitus, hypertriglyceridemia, and coronary artery disease. One pathogenetic factor of LD is dysregulation of several adipokines. However, the insulin resistance- and dyslipidemia-promoting adipokines adipocyte (AFABP) and epidermal (EFABP) fatty acid-binding protein have not been investigated in non-HIV-associated LD so far., Material and Methods: We performed a cross-sectional analysis of AFABP and EFABP serum concentrations in 37 LD patients and 37 age-, gender-, and body mass index-matched healthy controls. Moreover, AFABP and EFABP were correlated to clinical and biochemical parameters of inflammation, glucose control, and lipid metabolism., Results: There was no significant difference in median circulating AFABP and EFABP levels between LD patients (21.7μg/l and 7.5μg/l, respectively) and healthy controls (24.5μg/l and 8.6μg/l, respectively). Neither AFABP nor EFABP were related to markers of impaired glucose control or lipid metabolism. Multiple linear regression analysis showed a positive and independent association of AFABP with gender, serum leptin levels, and body mass index., Conclusions: Circulating levels of AFABP and EFABP are not decreased in LD despite adipose tissue loss in contrast to other adipokines including leptin and adiponectin., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far., Methods: Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD., Results: Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation., Conclusions: Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lipodystrophy (LD) is a rare disease with a paucity of subcutaneous adipocytes and leptin deficiency. Patients often develop severe diabetes and, additionally, show a disturbed eating behavior with reduced satiety. The disturbed eating behavior can be restored by substitution with the leptin analog metreleptin. Long-term effects of metreleptin on resting state brain connectivity in treatment-naive patients with LD have not been assessed. In this study, resting state functional MRI scans and extensive behavioral testing assessing changes in hunger/satiety regulation were performed during the first 52 weeks of metreleptin treatment in nine patients with LD. Resting state connectivity significantly increased over the course of metreleptin treatment in three brain areas (i.e., hypothalamus, insula/superior temporal gyrus, medial prefrontal cortex). Behavioral tests demonstrated that perceived hunger, importance of eating, eating frequencies, and liking ratings of food pictures significantly decreased during metreleptin therapy. Taken together, leptin substitution was accompanied by long-term changes of hedonic and homeostatic central nervous networks regulating eating behavior as well as decreased hunger feelings and diminished incentive value of food. Future studies need to assess whether metreleptin treatment in LD restores physiological processes important for the development of satiety., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Recently, exciting progress has been made in understanding the role of the CNS in controlling eating behaviour and in the development of overeating. Regions and networks of the human brain involved in eating behaviour and appetite control have been identified with neuroimaging techniques such as functional MRI, PET, electroencephalography, and magnetoencephalography. Hormones that regulate our drive to eat (eg, leptin, insulin, and glucagon-like peptide-1) can affect brain function. Defects in central hunger signalling are present in many pathologies. On the basis of an understanding of brain mechanisms that lead to overeating, powerful neuroimaging protocols could be a future clinical approach to allow individually tailored treatment options for patients with obesity. The aim of our Review is to provide an overview of neuroimaging approaches for obesity (ie, neuroimaging study design, questions which can be answered by neuroimaging, and limitations of neuroimaging techniques), examine current models of central nervous processes regulating eating behaviour, summarise and review important neuroimaging studies investigating therapeutic approaches to treat obesity or to control eating behaviour, and to provide a perspective on how neuroimaging might lead to new therapeutic approaches to obesity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)