@phdthesis{Graja2017,
  author    = {Graja, Antonia},
  title     = {Aging-related changes of progenitor cell function and microenvironment impair brown adipose tissue regeneration},
  school      = {Universit{\"a}t Potsdam},
  pages     = {152},
  year      = {2017},
  language  = {en}
}
@phdthesis{Weitkunat2017,
  author    = {Weitkunat, Karolin},
  title     = {Dietary fibers and short-chain fatty acids in the development of diet-induced obesity},
  school      = {Universit{\"a}t Potsdam},
  pages     = {121},
  year      = {2017},
  language  = {en}
}
@phdthesis{Jank2017,
  author    = {Jank, Anne-Marie},
  title     = {Effects of senescence on microenvironment-progenitor cell interaction},
  school      = {Universit{\"a}t Potsdam},
  pages     = {156},
  year      = {2017},
  language  = {en}
}
@phdthesis{Kasch2017,
  author    = {Kasch, Juliane},
  title     = {Impact of maternal high-fat consumption on offspring exercise performance, skeletal muscle energy metabolism, and obesity susceptibility},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-409703},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XII, 95, XXV},
  year      = {2017},
  abstract  = {Background: Obesity is thought to be the consequence of an unhealthy nutrition and a lack of physical activity. Although the resulting metabolic alterations such as impaired glucose homeostasis and insulin sensitivity can usually be improved by physical activity, some obese patients fail to enhance skeletal muscle metabolic health with exercise training. Since this might be largely heritable, maternal nutrition during pregnancy and lactation is hypothesized to impair offspring skeletal muscle physiology. Objectives: This PhD thesis aims to investigate the consequences of maternal high-fat diet (mHFD) consumption on offspring skeletal muscle physiology and exercise performance. We could show that maternal high-fat diet during gestation and lactation decreases the offspring's training efficiency and endurance performance by influencing the epigenetic profile of their skeletal muscle and altering the adaptation to an acute exercise bout, which in long-term, increases offspring obesity susceptibility. Experimental setup: To investigate this issue in detail, we conducted several studies with a similar maternal feeding regime. Dams (C57BL/6J) were either fed a low-fat diet (LFD; 10 energy\% from fat) or high-fat diet (HFD; 40 energy\% from fat) during pregnancy and lactation. After weaning, male offspring of both maternal groups were switched to a LFD, on which they remained until sacrifice in week 6, 15 or 25. In one study, LFD feeding was followed by HFD provision from week 15 until week 25 to elucidate the effects on offspring obesity susceptibility. In week 7, all mice were randomly allocated to a sedentary group (without running wheel) or an exercised group (with running wheel for voluntary exercise training). Additionally, treadmill endurance tests were conducted to investigate training performance and efficiency. In order to uncover regulatory mechanisms, each study was combined with a specific analytical setup, such as whole genome microarray analysis, gene and protein expression analysis, DNA methylation analyses, and enzyme activity assays. Results: mHFD offspring displayed a reduced training efficiency and endurance capacity. This was not due to an altered skeletal muscle phenotype with changes in fiber size, number, and type. DNA methylation measurements in 6 week old offspring showed a hypomethylation of the Nr4a1 gene in mHFD offspring leading to an increased gene expression. Since Nr4a1 plays an important role in the regulation of skeletal muscle energy metabolism and early exercise adaptation, this could affect offspring training efficiency and exercise performance in later life. Investigation of the acute response to exercise showed that mHFD offspring displayed a reduced gene expression of vascularization markers (Hif1a, Vegfb, etc) pointing towards a reduced angiogenesis which could possibly contribute to their reduced endurance capacity. Furthermore, an impaired glucose utilization of skeletal muscle during the acute exercise bout by an impaired skeletal muscle glucose handling was evidenced by higher blood glucose levels, lower GLUT4 translocation and diminished Lactate dehydrogenase activity in mHFD offspring immediately after the endurance test. These points towards a disturbed use of glucose as a substrate during endurance exercise. Prolonged HFD feeding during adulthood increases offspring fat mass gain in mHFD offspring compared to offspring from low-fat fed mothers and also reduces their insulin sensitivity pointing towards a higher obesity and diabetes susceptibility despite exercise training. Consequently, mHFD reduces offspring responsiveness to the beneficial effects of voluntary exercise training. Conclusion: The results of this PhD thesis demonstrate that mHFD consumption impairs the offspring's training efficiency and endurance capacity, and reduced the beneficial effects of exercise on the development of diet-induced obesity and insulin resistance in the offspring. This might be due to changes in skeletal muscle epigenetic profile and/or an impaired skeletal muscle angiogenesis and glucose utilization during an acute exercise bout, which could contribute to a disturbed adaptive response to exercise training.},
  language  = {en}
}
@phdthesis{Wittenbecher2017,
  author    = {Wittenbecher, Clemens},
  title     = {Linking whole-grain bread, coffee, and red meat to the risk of type 2 diabetes},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404592},
  school      = {Universit{\"a}t Potsdam},
  pages     = {XII, 194, ii},
  year      = {2017},
  abstract  = {Background: Consumption of whole-grain, coffee, and red meat were consistently related to the risk of developing type 2 diabetes in prospective cohort studies, but potentially underlying biological mechanisms are not well understood. Metabolomics profiles were shown to be sensitive to these dietary exposures, and at the same time to be informative with respect to the risk of type 2 diabetes. Moreover, graphical network-models were demonstrated to reflect the biological processes underlying high-dimensional metabolomics profiles. Aim: The aim of this study was to infer hypotheses on the biological mechanisms that link consumption of whole-grain bread, coffee, and red meat, respectively, to the risk of developing type 2 diabetes. More specifically, it was aimed to consider network models of amino acid and lipid profiles as potential mediators of these risk-relations. Study population: Analyses were conducted in the prospective EPIC-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2731, including 692 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Concentrations of 126 metabolites (acylcarnitines, phosphatidylcholines, sphingomyelins, amino acids) were determined in baseline-serum samples. Incident type 2 diabetes cases were assed and validated in an active follow-up procedure. The median follow-up time was 6.6 years. Analytical design: The methodological approach was conceptually based on counterfactual causal inference theory. Observations on the network-encoded conditional independence structure restricted the space of possible causal explanations of observed metabolomics-data patterns. Given basic directionality assumptions (diet affects metabolism; metabolism affects future diabetes incidence), adjustment for a subset of direct neighbours was sufficient to consistently estimate network-independent direct effects. Further model-specification, however, was limited due to missing directionality information on the links between metabolites. Therefore, a multi-model approach was applied to infer the bounds of possible direct effects. All metabolite-exposure links and metabolite-outcome links, respectively, were classified into one of three categories: direct effect, ambiguous (some models indicated an effect others not), and no-effect. Cross-sectional and longitudinal relations were evaluated in multivariable-adjusted linear regression and Cox proportional hazard regression models, respectively. Models were comprehensively adjusted for age, sex, body mass index, prevalence of hypertension, dietary and lifestyle factors, and medication. Results: Consumption of whole-grain bread was related to lower levels of several lipid metabolites with saturated and monounsaturated fatty acids. Coffee was related to lower aromatic and branched-chain amino acids, and had potential effects on the fatty acid profile within lipid classes. Red meat was linked to lower glycine levels and was related to higher circulating concentrations of branched-chain amino acids. In addition, potential marked effects of red meat consumption on the fatty acid composition within the investigated lipid classes were identified. Moreover, potential beneficial and adverse direct effects of metabolites on type 2 diabetes risk were detected. Aromatic amino acids and lipid metabolites with even-chain saturated (C14-C18) and with specific polyunsaturated fatty acids had adverse effects on type 2 diabetes risk. Glycine, glutamine, and lipid metabolites with monounsaturated fatty acids and with other species of polyunsaturated fatty acids were classified as having direct beneficial effects on type 2 diabetes risk. Potential mediators of the diet-diabetes links were identified by graphically overlaying this information in network models. Mediation analyses revealed that effects on lipid metabolites could potentially explain about one fourth of the whole-grain bread effect on type 2 diabetes risk; and that effects of coffee and red meat consumption on amino acid and lipid profiles could potentially explain about two thirds of the altered type 2 diabetes risk linked to these dietary exposures. Conclusion: An algorithm was developed that is capable to integrate single external variables (continuous exposures, survival time) and high-dimensional metabolomics-data in a joint graphical model. Application to the EPIC-Potsdam cohort study revealed that the observed conditional independence patterns were consistent with the a priori mediation hypothesis: Early effects on lipid and amino acid metabolism had the potential to explain large parts of the link between three of the most widely discussed diabetes-related dietary exposures and the risk of developing type 2 diabetes.},
  language  = {en}
}
@phdthesis{Eckel2017,
  author    = {Eckel, Nathalie},
  title     = {Metabolically healthy obesity and metabolically unhealthy normal weight - identification and associated risks},
  school      = {Universit{\"a}t Potsdam},
  pages     = {177},
  year      = {2017},
  language  = {en}
}
@phdthesis{Jannasch2017,
  author    = {Jannasch, Franziska},
  title     = {Methodological aspects of the derivation of dietary patterns and their association with type 2 diabetes},
  school      = {Universit{\"a}t Potsdam},
  pages     = {X, 205},
  year      = {2017},
  abstract  = {Hintergrund: Die Untersuchung von Ern{\"a}hrungsmustern als komplement{\"a}rer Ansatz zu der Untersuchung einzelner Lebensmittel nimmt stetig zu. Generell k{\"o}nnen drei verschiedene Ans{\"a}tze unterschieden werden um Ern{\"a}hrungsmuster herzuleiten: A priori Indizes, welche das Wissen {\"u}ber gesundheitsf{\"o}rderliche und -sch{\"a}dliche Eigenschaften eines Lebensmittels f{\"u}r einen gewissen Endpunkt nutzen; A posteriori (exploratorische) Ern{\"a}hrungsmuster, welche die populationsspezifischen vorliegenden Daten ohne eine vorangegangene Hypothese nutzen; gemischte Methoden, die das Wissen {\"u}ber bestimmte N{\"a}hrstoffe oder Biomarker, welche in der Krankheitsentstehung eine Rolle spielen, nutzen und mit einer exploratorischen Methode kombinieren um krankheitsrelevante Ern{\"a}hrungsmuster zu generieren. Vorangegangene systematische {\"U}bersichtsarbeiten, welche die Evidenz der Assoziation zwischen Ern{\"a}hrungsmustern und Diabetes mellitus Typ 2 zusammenfassten, waren entweder beschr{\"a}nkt auf eine Mustermethode oder kombinierten die Muster verschiedener Methoden, ohne die Zusammensetzung der Ern{\"a}hrungsmuster zu ber{\"u}cksichtigen. Ziel: Das Ziel dieser Dissertation war eine umfassende Untersuchung der Assoziation von Ern{\"a}hrungsmustern mit Diabetes mellitus Typ 2. Das erste Teilprojekt zielte auf die Erstellung einer systematischen {\"U}bersichtsarbeit von prospektiven Studien ab, unter der Ber{\"u}cksichtigung der verschiedenen Methoden zur Herleitung von Ern{\"a}hrungsmustern in der meta-analytischen Zusammenfassung, was in vorangegangen {\"U}bersichtsarbeiten eine Limitation darstellte. Das zweite Teilprojekt hatte die Untersuchung der Assoziation mit Diabetes mellitus Typ 2 von exploratorischen Ern{\"a}hrungsmustern, welche mit der Hauptkomponentenanalyse in einer multi-zentrischen europ{\"a}ischen Fall-Kohorten Studie hergeleitet wurden, zum Ziel. Des Weiteren wurde der eingeschr{\"a}nkten Anwendbarkeit von exploratorischen Mustern in anderen Studienpopulationen mit Methoden der Replikation dieser Ern{\"a}hrungsmuster begegnet. Methoden: Im ersten Teilprojekt wurde eine systematische Literatursuche in den Datenbanken MEDLINE und Web of Science vorgenommen, sowie ein dreistufiger Screeningprozess. Die identifizierten Studien wurden nach den jeweiligen Methoden zur Erstellung von Ern{\"a}hrungsmustern zusammengefasst und Meta-Analysen nur f{\"u}r diejenigen Ern{\"a}hrungsmuster mit vergleichbarer Zusammensetzung vorgenommen. Im zweiten Teilprojekt wurden l{\"a}nderspezifische Ern{\"a}hrungsmuster mittels Hauptkomponentenanalyse aus 36 standardisierten Lebensmittelgruppen hergeleitet. Die Assoziation mit Diabetes mellitus Typ 2 Risiko wurde mit verschieden adjustierten Cox Regressionsmodellen zur Berechnung von Hazardratenverh{\"a}ltnissen untersucht. Die Ern{\"a}hrungsmuster, welche eine signifikante Assoziation mit dem Diabetesrisiko aufzeigten, wurden anschließend {\"u}ber alle L{\"a}nder in der EPIC-InterAct Studie repliziert: Entweder wurden Summenscores ungewichteter standardisierter Lebensmittelgruppen berechnet (wenn die Korrelation mit dem originalen Ern{\"a}hrungsmuster r ≥ 0.90 war) oder Summenscores der Produkte von standardisierten Scoringkoeffizienten mit standardisierten Lebensmittelgruppen (wenn die Korrelation mit dem originalen Ern{\"a}hrungsmuster r < 0.90). Die resultierenden Scores wurden standardisiert nach der Verteilung der gesamten EPIC-InterAct Subkohorte, dann in jedem Land angewendet und die Assoziation mit Diabetes mellitus Typ 2 anhand der Cox Regressionsmodelle berechnet. Anschließend wurden Meta-Analysen zur Berechnung der gepoolten Sch{\"a}tzer durchgef{\"u}hrt. Ergebnisse: Im ersten Teilprojekt ergab die Literatursuche 48 Artikel, welche 16 Kohorten umfassten. Die Einhaltung der Mediterranen Di{\"a}t (relatives Risiko (RR) f{\"u}r den Vergleich der extremen Quantile: 0,87; 95\%-Konfidenzintervall (KI): 0,82, 0,93), der DASH Di{\"a}t (RR: 0,81; 95\%-KI: 0,72, 0,92) und des Alternative Healthy Eating Index (AHEI) (RR: 0,79; 95\%-KI: 0,69, 0,90) war mit einer signifikanten Reduzierung des Diabetesrisikos assoziiert. Exploratorische Ern{\"a}hrungsmuster, charakterisiert durch rotes und verarbeitetes Fleisch, prozessiertes Getreide, hochfette Milchprodukte, Eier und frittierte Produkte, waren positiv mit dem Diabetesrisiko assoziiert (RR: 1,44; 95\%-KI: 1,27, 1,62), w{\"a}hrend Ern{\"a}hrungs-muster, charakterisiert durch Gem{\"u}se, H{\"u}lsenfr{\"u}chte, Obst, Gefl{\"u}gel und Fisch, invers mit dem Diabetesrisiko assoziiert waren (RR: 0,84; 95\%-KI: 0,77, 0,91). Ern{\"a}hrungsmuster, welche mit reduzierter Rangregression hergeleitet wurden und charakterisiert waren durch eine hohe Aufnahme von prozessiertem Getreide, zuckerges{\"u}ßten Getr{\"a}nken und verarbeitetem Fleisch und einen niedrigen Weinkonsum, waren alle signifikant mit dem Diabetesrisiko assoziiert. Im zweiten Teilprojekt konnten zwei wesentliche Ern{\"a}hrungsmuster in jedem Land mit der Hauptkomponentenanalyse hergeleitet werden. Ein Ern{\"a}hrungsmuster, welches in Frankreich hergeleitet wurde und charakterisiert war durch N{\"u}sse, andere Fr{\"u}chte, verarbeitetes Fleisch, Fisch, Eier, Kuchen und Kekse, Kaffee und andere alkoholische Getr{\"a}nke, war signifikant assoziiert mit einem erniedrigten Diabetesrisiko. Drei andere Ern{\"a}hrungsmuster, hergeleitet in Spanien, Norfolk und Oxford, welche sich erheblich in ihrer Zusammensetzung unterschieden, waren mit einem erh{\"o}hten Diabetesrisiko assoziiert. Keine der Replikationen dieser vier Ern{\"a}hrungsmuster konnte die signifikante Assoziation mit Diabetes mellitus Typ 2 {\"u}ber andere L{\"a}nder best{\"a}tigen. Schlussfolgerung: Aus der systematischen {\"U}bersichtsarbeit ließ sich schlussfolgern, dass Ern{\"a}hrungsweisen gem{\"a}ß der Mediterranen Di{\"a}t, DASH und AHEI ein starkes Potenzial zur Pr{\"a}vention von Diabetes mellitus Typ 2 zu haben, obwohl sie sich in einigen Komponenten unterscheiden. Exploratorische Ern{\"a}hrungsmuster wurden basierend auf konkordanten Lebensmitteln gruppiert und waren signifikant mit dem Diabetesrisiko assoziiert, auch wenn die Untersuchungen einzelner Lebensmittel eher begrenzte Evidenz f{\"u}r einen Zusammenhang aufwiesen. Trotzdem bleiben sie populationsspezifische Beobachtungen. Das wurde auch in dem zweiten Teilprojekt unterstrichen, als l{\"a}nderspezifische Ern{\"a}hrungsmuster generiert wurden und keines der Ern{\"a}hrungsmuster, welches signifikant mit dem Diabetesrisiko assoziiert war, durch Simplifizierung oder Replikation der Musterstruktur des Originalmusters {\"u}ber alle L{\"a}nder best{\"a}tigt werden konnte. F{\"u}r drei RRR-Muster konnten konsistente positive Assoziationen mit dem Diabetesrisiko {\"u}ber verschiedene Studienpopulationen beobachtet werden.},
  language  = {en}
}
@phdthesis{Roediger2017,
  author    = {R{\"o}diger, Maria},
  title     = {The Impact of the ARFRP1 Action at the Golgi Apparatus on Adipocyte Function},
  school      = {Universit{\"a}t Potsdam},
  pages     = {116},
  year      = {2017},
  language  = {en}
}
@phdthesis{Stadion2017,
  author    = {Stadion, Mandy},
  title     = {Validation and Characterization of lfi202b and Zfp69, two Novel Disease Genes in Obesity-Associated Insulin Resistance},
  school      = {Universit{\"a}t Potsdam},
  pages     = {158},
  year      = {2017},
  language  = {en}
}