@phdthesis{Leicht2008, author = {Leicht, Katja}, title = {Positionelle Klonierung von Tbc1d1 als Kandidatengen f{\"u}r Adipositas}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-34610}, school = {Universit{\"a}t Potsdam}, year = {2008}, abstract = {Nob1 (New Zealand obese 1) bezeichnet einen Adipositas-QTL auf Chr. 5 der Maus (LODBMI >3,3), der in einem R{\"u}ckkreuzungsexperiment der Mausst{\"a}mme NZO (adip{\"o}s) und SJL (schlank) identifiziert wurde. Um Kandidatengene f{\"u}r Adipositas zu finden, wurden mehr als 300 Nob1-Transkripte mit Hilfe von Genexpressionsanalysen auf Unterschiede in stoffwechselrelevanten Geweben zwischen beiden Mausst{\"a}mmen untersucht. Sieben Gene zeigten eine differentielle Expression: 2310045A20Rik, Tbc1d1, Ppp1cb, Mll5, Insig1, Abhd1 und Alox5ap. Die codierenden Bereiche dieser Gene wurden anschließend auf Sequenzunterschiede zwischen NZO und SJL untersucht. Nur im Gen Tbc1d1, das im Peak-Bereich des Nob1 lokalisiert ist, wurde eine SJL-spezifische Deletion von sieben Basen detektiert, die zu einer Leserasterverschiebung und einem vorzeitigen Abbruch des Proteins in der funktionellen Rab-GAP-Dom{\"a}ne f{\"u}hrt (Loss-of-Function-Mutation). Interessanterweise wurde eine Variante von TBC1D1 (R125W) in Kopplungsanalysen mit Adipositas beim Menschen assoziiert (Stone et al., 2006). TBC1D1 zeigt eine hohe Homologie zu TBC1D4 (AS160), das im Insulinsignalweg eine wichtige Rolle spielt. In 17 weiteren Genen im Peak-Bereich des Nob1 wurde keine weitere SJL-spezifischen Mutation detektiert. Bei NZO-Tieren erfolgte die Tbc1d1-mRNA-Expression vorwiegend in glycolytischen Fasern des Skelettmuskels. Zudem wurden zwei gewebsspezifisch exprimierte Tbc1d1-Isoformen identifiziert, die sich durch alternatives Splicen der Exone 12 und 13 unterscheiden. Die im Rahmen dieser Arbeit gefundenen Ergebnisse machen Tbc1d1 zu einem plausiblen Kandidatengen f{\"u}r den Nob1-QTL. Welche Funktion Tbc1d1 im Glucose- und Fettstoffwechsel des Skelettmuskels hat, muss in weiteren Analysen untersucht werden.}, language = {de} } @phdthesis{Andres2008, author = {Andres, Janin}, title = {Untersuchungen {\"u}ber Regulationsmechanismen der 11beta-Hydroxysteroid Dehydrogenase Typ 1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-33033}, school = {Universit{\"a}t Potsdam}, year = {2008}, abstract = {Die 11beta-HSD1 reguliert intrazellul{\"a}r die Cortisolkonzentration durch Regeneration von Cortison z.B. aus dem Blutkreislauf, zu Cortisol. Daher stellt diese ein wichtiges Element in der Glucocorticoid-vermittelten Genregulation dar. Die 11beta-HSD1 wird ubiquit{\"a}r exprimiert, auf hohem Niveau besonders in Leber, Fettgewebe und glatten Muskelzellen. Insbesondere die Bedeutung der 11beta-HSD1 in Leber und Fettgewebe konnte mehrfach nachgewiesen werden. In der Leber f{\"u}hrte eine erh{\"o}hte Aktivit{\"a}t aufgrund einer {\"U}berexpression in M{\"a}usen zu einer verst{\"a}rkten Gluconeogeneserate. Des Weiteren konnte gezeigt werden, dass eine erh{\"o}hte Expression und erh{\"o}hte Enzymaktivit{\"a}t der 11beta-HSD1 im subkutanen und viszeralen Fettgewebe assoziiert ist mit Fettleibigkeit, Insulinresistenz und Dyslipid{\"a}mie. {\"U}ber die Regulation ist jedoch noch wenig bekannt. Zur Untersuchung der Promotoraktivit{\"a}t wurde der Promotorbereich von -3034 bis +188, vor und nach dem Translations- und Transkriptionsstart, der 11beta-HSD1 kloniert. 8 Promotorfragmente wurden mittels Dual-Luciferase-Assay in humanen HepG2-Zellen sowie undifferenzierten und differenzierten murinen 3T3-L1-Zellen untersucht. Anschließend wurde mittels nicht-radioaktiven EMSA die Bindung des TATA-Binding Proteins (TBP) sowie von CCAAT/Enhancer-Binding-Proteinen (C/EBP) an ausgew{\"a}hlte Promotorregionen analysiert. Nach der Charakterisierung des Promotors wurden spezifische endogene und exogene Regulatoren untersucht. Fetts{\"a}uren modifizieren die Entstehung von Adipositas und Insulinresistenz. Ihre Wirkung wird u.a. PPARgamma-abh{\"a}ngig vermittelt und kann durch das Inkretin (Glucose-dependent insulinotropic Peptide) GIP modifiziert werden. So wurden die Effekte von unterschiedlichen Fetts{\"a}uren, vom PPARgamma Agonisten Rosiglitazon sowie dem Inkretin GIP auf die Expression und Enzymaktivit{\"a}t der 11beta-HSD1 untersucht. Dies wurde in-vitro-, tierexperimentell und in humanen in-vivo-Studien realisiert. Zuletzt wurden 2 Single Nucleotide Polymorphismen (SNP) im Promotorbereich der 11beta-HSD1 in der Zellkultur im Hinblick auf potentielle Funktionalit{\"a}t analysiert sowie die Assoziation mit Diabetes mellitus Typ 2 und K{\"o}rpergewicht in der MeSyBePo-Kohorte bei rund 1.800 Personen untersucht. Die Luciferase-Assays zeigten basal eine zell-spezifische Regulation der 11beta-HSD1, wobei in allen 3 untersuchten Zelltypen die Bindung eines Repressors nachgewiesen werden konnte. Zudem konnte eine m{\"o}gliche Bindung des TBPs sowie von C/EBP-Proteinen an verschiedene Positionen gezeigt werden. Die Transaktivierungsassays mit den C/EBP-Proteinen -alpha, -beta und -delta zeigten eben-falls eine zellspezifische Regulation des 11beta-HSD1-Promotors. Die Aktivit{\"a}t und Expression der 11beta-HSD1 wurde durch die hier untersuchten endogenen und exogenen Faktoren spezifisch modifiziert, was sowohl in-vitro als auch in-vivo in unterschiedlichen Modellsystemen dargestellt werden konnte. Die Charakterisierung der MeSyBePo-Kohorte ergab keine direkten Assoziationen zwischen Polymorphismus und klinischem Ph{\"a}notyp, jedoch Tendenzen f{\"u}r eine erh{\"o}htes K{\"o}rper-gewicht und Typ 2 Diabetes mellitus in Abh{\"a}ngigkeit des Genotyps. Der Promotor der 11beta-HSD1 konnte aufgrund der Daten aus den Luciferaseassays sowie den Daten aus den EMSA-Analysen n{\"a}her charakterisiert werden. Dieser zeigt eine variable und zell-spezifische Regulation. Ein wichtiger Regulator stellen insbesondere in den HepG2-Zellen die C/EBP-Proteine -alpha, -beta und -delta dar. Aus den in-vivo-Studien ergab sich eine Regulation der 11beta-HSD1 durch endogene, exogene und pharmakologische Substanzen, die durch die Zellkulturversuche best{\"a}tigt und n{\"a}her charakterisiert werden konnten.}, language = {de} } @article{WarschburgerKroeller2012, author = {Warschburger, Petra and Kr{\"o}ller, Katja}, title = {"Childhood overweight and obesity maternal perceptions of the time for engaging in child weight management"}, series = {BMC public health}, volume = {12}, journal = {BMC public health}, number = {12}, publisher = {BioMed Central}, address = {London}, issn = {1471-2458}, doi = {10.1186/1471-2458-12-295}, pages = {8}, year = {2012}, abstract = {Background: There is an increasing awareness of the impact of parental risk perception on the weight course of the child and the parent's readiness to engage in preventive efforts, but only less is known about factors related to the parental perception of the right time for the implementation of preventive activities. The aim of this study was to examine parental perceptions of the appropriate time to engage in child weight management strategies, and the factors associated with different weight points at which mothers recognize the need for preventive actions. Methods: 352 mothers with children aged 2-10 years took part in the study. We assessed mothers' perceptions of the actual and preferred weight status of their child, their ability to identify overweight and knowledge of its associated health risks, as well as perceptions of the right time for action to prevent overweight in their child. A regression analysis was conducted to examine whether demographic and weight related factors as well as the maternal general risk perception were associated with recognizing the need to implement prevention strategies. Results: Although most of the parents considered a BMI in the 75th to 90th percentile a valid reason to engage in the prevention of overweight, 19\% of the mothers were not willing to engage in prevention until their child reached the 97th percentile. Whereas the child's sex and the identification of an elevated BMI were significant predictors for parents' recognition of the 75th percentile as right point to engage in prevention efforts, an inability to recognize physical health risks associated with overweight silhouettes emerged as a significant factor predicting which parents would delay prevention efforts until a child's BMI reached the 97th percentile. Conclusion: Parental misperceptions of overweight and associated health risks constitute unfavorable conditions for preventive actions. Feedback on the health risks associated with overweight could help increase maternal readiness for change.}, language = {en} } @article{CaliendoLee2013, author = {Caliendo, Marco and Lee, Wang-Sheng}, title = {Fat chance! - Obesity and the transition from unemployment to employment}, series = {Economics and human biology}, volume = {11}, journal = {Economics and human biology}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1570-677X}, doi = {10.1016/j.ehb.2012.02.002}, pages = {121 -- 133}, year = {2013}, abstract = {This paper focuses on estimating the magnitude of any potential weight discrimination by examining whether obese job applicants in Germany get treated or behave differently from non-obese applicants. Based on two waves of rich survey data from the IZA Evaluation dataset, which includes measures that control for education, demographic characteristics, labor market history, psychological factors and health, we estimate differences in job search behavior and labor market outcomes between obese/overweight and normal weight individuals. Unlike other observational studies which are generally based on obese and non-obese individuals who might already be at different points in the job ladder (e.g., household surveys), in our data, individuals are newly unemployed and all start from the same point. The only subgroup we find in our data experiencing any possible form of negative labor market outcomes is obese women. Despite making more job applications and engaging more in job training programs, we find some indications that they experienced worse (or at best similar) employment outcomes than normal weight women. Obese women who found a job also had significantly lower wages than normal weight women.}, language = {en} } @article{WarschburgerKuhne2014, author = {Warschburger, Petra and Kuhne, Daniela}, title = {Psychosocial determinants of quality of life in parents of obese children seeking inpatient treatment}, series = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {23}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, number = {7}, publisher = {Springer}, address = {Dordrecht}, issn = {0962-9343}, doi = {10.1007/s11136-014-0659-y}, pages = {1985 -- 1995}, year = {2014}, abstract = {To examine and identify predictors of parental health-related quality of life (HRQoL) in a sample of obese and very obese children participating in an inpatient program for treating obesity.}, language = {en} } @article{MummSchefflerHermanussen2014, author = {Mumm, Rebekka and Scheffler, Christiane and Hermanussen, Michael}, title = {Developing differential height, weight and body mass index references for girls that reflect the impact of the menarche}, series = {Acta paediatrica : nurturing the child}, volume = {103}, journal = {Acta paediatrica : nurturing the child}, number = {7}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0803-5253}, doi = {10.1111/apa.12625}, pages = {e312 -- e316}, year = {2014}, abstract = {Aim Growth is both a matter of amplitude and tempo. We aimed to develop references for body height, body weight and body mass index (BMI) with respect to tempo of maturity. Methods Data obtained from the German KiGGS study (2003-2006) on body height, body weight and presence or absence of the menarche were re-analysed in 3776 girls, aged 10-17years. We developed smoothed centiles for BMI-, body-height- and body-weight-for-age using the LMS method for premenarcheal and postmenarcheal girls. Results Body height, body weight and BMI differed significantly between premenarcheal and postmenarcheal girls. On average, postmenarcheal girls aged 11-17years were 5.3cm taller and 9.7kg heavier, and their BMI was 2.9kg/m2 higher than in premenarcheal girls of the same calendar age. Conclusion Adolescent BMI rises with calendar age and biological age. New reference charts for adolescent girls aged 10-18years were generated to be inserted into the currently used references to avoid misclassifying underweight and overweight pubertal girls.}, language = {en} } @article{HoffmannWarschburger2015, author = {Hoffmann, Svenja and Warschburger, Petra}, title = {Body image in obese children and adolescents. Body dissatisfaction and body size perception in relation to quality of life and weight loss}, series = {Psychotherapeut}, volume = {60}, journal = {Psychotherapeut}, number = {6}, publisher = {Springer}, address = {New York}, issn = {0935-6185}, doi = {10.1007/s00278-015-0060-5}, pages = {498 -- 504}, year = {2015}, abstract = {Body dissatisfaction and an unrealistic perception of own body size are particularly common in obese children and adolescents; however, little is known about the association with weight-related quality of life and the impact on successful long-term weight loss. At the beginning of an inpatient child obesity rehabilitation program, 408 children and adolescents aged 9-12 years completed a questionnaire on body image (body silhouettes) and a body weight-specific questionnaire for overweight and obese children and adolescents (GW-LQ-KJ) on quality of life. Height and weight were measured by a physician at the beginning and 1 year after inpatient hospitalization. Of the participants 91.9 \% reported body dissatisfaction and 75.7 \% underestimated their own body size. There were no gender-specific differences in body dissatisfaction but boys perceived their body size more realistically than girls. Participants with body dissatisfaction and realistic body size perception showed a reduced weight-related quality of life. Those participants who realistically perceived their body size also lost less weight in the long term. The subjective underestimation of body size proved to be important for reduced weight-related quality of life and more pronounced long-term weight loss; therefore, body image should be taken into account in multimodal treatment programs.}, language = {de} } @article{Warschburger2015, author = {Warschburger, Petra}, title = {SRT-Joy - computer-assisted self-regulation training for obese children and adolescents: study protocol for a randomized controlled trial}, series = {Trials}, volume = {16}, journal = {Trials}, publisher = {BioMed Central}, address = {London}, issn = {1745-6215}, doi = {10.1186/s13063-015-1078-2}, pages = {10}, year = {2015}, abstract = {Background: Obesity is not only a highly prevalent disease but also poses a considerable burden on children and their families. Evidence is increasing that a lack of self-regulation skills may play a role in the etiology and maintenance of obesity. Our goal with this currently ongoing trial is to examine whether training that focuses on the enhancement of self-regulation skills may increase the sustainability of a complex lifestyle intervention. Methods/Design: In a multicenter, prospective, parallel group, randomized controlled superiority trial, 226 obese children and adolescents aged 8 to 16 years will be allocated either to a newly developed computer-training program to improve their self-regulation abilities or to a placebo control group. Randomization occurs centrally and blockwise at a 1:1 allocation ratio for each center. This study is performed in pediatric inpatient rehabilitation facilities specialized in the treatment of obesity. Observer-blind assessments of outcome variables take place at four times: at the beginning of the rehabilitation (pre), at the end of the training in the rehabilitation (post), and 6 and 12 months post-rehabilitation intervention. The primary outcome is the course of BMI-SDS over 1 year after the end of the inpatient rehabilitation. Secondary endpoints are the self-regulation skills. In addition, health-related quality of life, and snack intake will be analyzed. Discussion: The computer-based training programs might be a feasible and attractive tool to increase the sustainability of the weight loss reached during inpatient rehabilitation.}, language = {en} } @article{WarschburgerKroeller2016, author = {Warschburger, Petra and Kr{\"o}ller, Katja}, title = {Loss to follow-up in a randomized controlled trial study for pediatric weight management (EPOC)}, series = {BMC pediatrics}, volume = {16}, journal = {BMC pediatrics}, publisher = {BioMed Central}, address = {London}, issn = {1471-2431}, doi = {10.1186/s12887-016-0727-2}, pages = {9}, year = {2016}, abstract = {Background Attrition is a serious problem in intervention studies. The current study analyzed the attrition rate during follow-up in a randomized controlled pediatric weight management program (EPOC study) within a tertiary care setting. Methods Five hundred twenty-three parents and their 7-13-year-old children with obesity participated in the randomized controlled intervention trial. Follow-up data were assessed 6 and 12 months after the end of treatment. Attrition was defined as providing no objective weight data. Demographic and psychological baseline characteristics were used to predict attrition at 6- and 12-month follow-up using multivariate logistic regression analyses. Results Objective weight data were available for 49.6 (67.0) \% of the children 6 (12) months after the end of treatment. Completers and non-completers at the 6- and 12-month follow-up differed in the amount of weight loss during their inpatient stay, their initial BMI-SDS, educational level of the parents, and child's quality of life and well-being. Additionally, completers supported their child more than non-completers, and at the 12-month follow-up, families with a more structured eating environment were less likely to drop out. On a multivariate level, only educational background and structure of the eating environment remained significant. Conclusions The minor differences between the completers and the non-completers suggest that our retention strategies were successful. Further research should focus on prevention of attrition in families with a lower educational background.}, language = {en} } @misc{WarschburgerKroeller2016, author = {Warschburger, Petra and Kr{\"o}ller, Katja}, title = {Loss to follow-up in a randomized controlled trial study for pediatric weight management (EPOC)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-100359}, pages = {9}, year = {2016}, abstract = {Background Attrition is a serious problem in intervention studies. The current study analyzed the attrition rate during follow-up in a randomized controlled pediatric weight management program (EPOC study) within a tertiary care setting. Methods Five hundred twenty-three parents and their 7-13-year-old children with obesity participated in the randomized controlled intervention trial. Follow-up data were assessed 6 and 12 months after the end of treatment. Attrition was defined as providing no objective weight data. Demographic and psychological baseline characteristics were used to predict attrition at 6- and 12-month follow-up using multivariate logistic regression analyses. Results Objective weight data were available for 49.6 (67.0) \% of the children 6 (12) months after the end of treatment. Completers and non-completers at the 6- and 12-month follow-up differed in the amount of weight loss during their inpatient stay, their initial BMI-SDS, educational level of the parents, and child's quality of life and well-being. Additionally, completers supported their child more than non-completers, and at the 12-month follow-up, families with a more structured eating environment were less likely to drop out. On a multivariate level, only educational background and structure of the eating environment remained significant. Conclusions The minor differences between the completers and the non-completers suggest that our retention strategies were successful. Further research should focus on prevention of attrition in families with a lower educational background.}, language = {en} }