TY - JOUR A1 - Miras, Alexander D. A1 - Seyfried, Florian A1 - Phinikaridou, Alkystis A1 - Andia, Marcelo E. A1 - Christakis, Ioannis A1 - Spector, Alan C. A1 - Botnar, Rene M. A1 - le Roux, Carel W. T1 - Rats Fed Diets with Different Energy Contribution from Fat Do Not Differ in Adiposity JF - OBESITY FACTS N2 - Objective: To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition. Methods: In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin. Results: In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments. Conclusions: We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it. (C) 2014 S Karger GmbH, Freiburg KW - Leptin KW - body fat KW - induced obesity KW - visceral fat KW - isocaloric intake KW - mass KW - tissue KW - weight-gain KW - metabolism KW - expenditure KW - accumulation KW - High-fat diet KW - Low-fat diet KW - MRI Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115249 VL - 7 IS - 5 ER - TY - JOUR A1 - Bensaad, Karim A1 - Favaro, Elena A1 - Lewis, Caroline A. A1 - Peck, Barrie A1 - Lord, Simon A1 - Collins, Jennifer M. A1 - Pinnick, Katherine E. A1 - Wigfield, Simon A1 - Buffa, Francesca M. A1 - Li, Ji-Liang A1 - Zhang, Qifeng A1 - Wakelam, Michael J. O. A1 - Karpe, Fredrik A1 - Schulze, Almut A1 - Harris, Adrian L. T1 - Fatty Acid Uptake and Lipid Storage Induced by HIF-1 alpha Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation JF - Cell Reports N2 - An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1 alpha (HIF-1 alpha)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O-2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via beta-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo. KW - inducible factor-I KW - binding protein KW - triglyceride accumulation KW - cancer cell KW - complex-III KW - beta-oxidation KW - metabolism KW - lipogenesis KW - proliferation KW - resistance Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115162 SN - 2211-1247 VL - 9 IS - 1 ER - TY - THES A1 - Schmalbach, Katja T1 - Identification of factors influencing 17beta-estradiol metabolism in female mammary gland T1 - Identifizierung von Einflussfaktoren auf den 17beta-Estradiolmetabolismus der weiblichen Brustdrüse N2 - The female sex hormone 17beta-estradiol, produced naturally in the body, seems to play an important role in the development of breast cancer, since (i) it can be activated to reactive metabolites, which are known to damage DNA and (ii) the stimulation of the estrogen receptor alpha by 17beta-estradiol enhances cell proliferation. Both processes together increase mutation frequency and subsequently lead to transformation of epithelial cells. Therefore, the aim of this work was to characterize the influence of polymorphisms and lifestyle factors on 17beta-estradiol metabolism in normal mammary gland tissue. [...] In sum, the tissue specific 17beta-estradiol metabolism was described in mammary gland tissue homogenate, whereas differences in proliferation of epithelial cells were only reflected in isolated epithelial cells. Factors associated with breast cancer risk (age, BMI and age-related changes in mammary gland morphology) were shown to affect 17beta-estradiol tissue levels. The 17beta-estradiol mediated genotoxicity was evaluated using bioinformatically calculated DNA adduct fluxes, which were predominately influenced by individual mRNA patterns rather than individual genotypes and (DNA adduct fluxes) were correlated with known breast cancer risk factors (age, parity, BMI and polymorphism of glutathione-S-transferase theta 1). N2 - Das körpereigene, weibliche Geschlechtshormon, 17beta-Estradiol spielt eine wichtige Rolle bei der Brustkrebsentstehung, da (i) es zu reaktiven Metaboliten aktiviert werden kann, welche die DNA schädigen können und (ii) durch die Stimulation des Estrogenrezeptors alpha die Zellproliferation steigern kann. Beide Prozesse können dann zum Anstieg der Mutationsfrequenz und anschließender maligner Transformation von Epithelzellen führen. Deshalb war das Ziel dieser Arbeit, den Einfluss von Polymorphismen und der Lebensweise auf den gewebespezifischen 17beta-Estradiol-Metabolismus im normalen Brustdrüsengewebe zu untersuchen. [...] Zusammenfassend wurde der gewebespezifische 17beta-Estradiol-Metabolismus in der weiblichen Brustdrüse beschrieben. Unterschiede in der Proliferation von Epithelzellen wurden nur in mittels Laser-Mikrodissektion isolierten Epithelzellen widergespiegelt. Es wurde gezeigt, dass Faktoren, die mit einem verändertem Brustkrebsrisiko assoziiert sind (Alter, BMI und altersbedingte Veränderungen in der Brustdrüsenmorphologie), den 17beta-Estradiol-Gewebespiegel in der Brustdrüse beeinflussen. Die 17beta-Estradiol-vermittelte Genotoxizität wurde mittels bioinformatischer Berechnung der DNA-Adduktflüsse ausgewertet, welche vornehmlich von den individuellen mRNA-Mustern beeinflusst wurde statt von dem individuellen Genotyp. Die DNA-Adduktflüsse korrelierten mit bekannten Brustkrebsrisiko-Faktoren (Alter, Parität, BMI und Polymorphismus der Glutathion-S-Transferase theta 1). KW - Milchdrüse KW - Estradiol KW - Präamplifizierung KW - metabolisches Netzwerk KW - 17beta-Estradiol KW - mRNA-Spiegel KW - mammary gland KW - mRNA level KW - metabolic network KW - 17beta-estradiol KW - metabolism KW - Stoffwechsel KW - Brustdrüse KW - Metabolismus Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-109300 ER -