@phdthesis{Radloff2018, author = {Radloff, Katrin}, title = {The role of the fatty acid profile and its modulation by cytokines in the systemic inflammation in cancer cachexia}, school = {Universit{\"a}t Potsdam}, pages = {156}, year = {2018}, abstract = {Systemic inflammation is a hallmark of cancer cachexia. Among tumor-host interactions, the white adipose tissue (WAT) is an important contributor to inflammation as it suffers morphological reorganization and lipolysis, releasing free fatty acids (FA), bioactive lipid mediators (LM) and pro-inflammatory cytokines, which accentuate the activation of pro-inflammatory signaling pathways and the recruitment of immune cells to the tissue. This project aimed to investigate which inflammatory factors are involved in the local adipose tissue inflammation and what is the influence of such factors upon enzymes involved in FA or LM metabolism in healthy individuals (Control), weight stable gastro-intestinal cancer patients (WSC) and cachectic cancer patients (CC). The results demonstrated that the inflammatory signature of systemic inflammation is different from local adipose tissue inflammation. The systemic inflammation of the cachectic cancer patients was characterized by higher levels of circulating saturated fatty acids (SFA), tumor-necrosis-factor-α (TNF-α), interleukins IL-6, IL-8 and CRP while levels of polyunsaturated fatty acids (PUFAs), especially n3-PUFAs, were lower in CC than in the other groups. In vitro and in adipose tissue explants, pro-inflammatory cytokines and SFAs were shown to increase the chemokines IL-8 and CXCL10 that were found to be augmented in adipose tissue inflammation in CC which was more profound in the visceral adipose tissue (VAT) than in subcutaneous adipose tissue (SAT). Systemic inflammation was negatively associated with the expression of PUFA synthesizing enzymes, though gene and protein expression did hardly differ between groups. The effects of inflammatory factors on enzymes in the whole tissue could have been masked by differentiated modulation of the diverse cell types in the same tissue. In vitro experiments showed that the expression of FA-modifying enzymes such as desaturases and elongases in adipocytes and macrophages was regulated into opposing directions by TNF-α, IL-6, LPS or palmitate. The higher plasma concentration of the pro-resolving LM resolvin D1 in CC cannot compensate the overall inflammatory status and the results indicate that inflammatory cytokines interfere with synthesis pathways of pro-resolving LM. In summary, the data revealed a complex inter-tissue and inter-cellular crosstalk mediated by pro-inflammatory cytokines and lipid compounds enhancing inflammation in cancer cachexia by feed-forward mechanisms.}, language = {en} } @article{HenkelAlfineSainetal.2018, author = {Henkel, Janin and Alfine, Eugenia and Sa{\´i}n, Juliana and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jos{\´e} Pedro and K{\"o}nig, Jeannette and Stuhlmann, Christin and Vahrenbrink, Madita and Jonas, Wenke and Kleinridders, Andr{\´e} and P{\"u}schel, Gerhard Paul}, title = {Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol}, series = {Nutrients}, volume = {10}, journal = {Nutrients}, number = {9}, publisher = {Molecular Diversity Preservation International (MDPI)}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu10091326}, pages = {1 -- 17}, year = {2018}, abstract = {While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.}, language = {en} } @article{WackerMarzetzSpijkerman2015, author = {Wacker, Alexander and Marzetz, Vanessa and Spijkerman, Elly}, title = {Interspecific competition in phytoplankton drives the availability of essential mineral and biochemical nutrients}, series = {Ecology : a publication of the Ecological Society of America}, volume = {96}, journal = {Ecology : a publication of the Ecological Society of America}, number = {9}, publisher = {Wiley}, address = {Washington}, issn = {0012-9658}, doi = {10.1890/14-1915.1}, pages = {2467 -- 2477}, year = {2015}, abstract = {The underlying mechanisms and consequences of competition and diversity are central themes in ecology. A higher diversity of primary producers often results in higher resource use efficiency in aquatic and terrestrial ecosystems. This may result in more food for consumers on one hand, while, on the other hand, it can also result in a decreased food quality for consumers; higher biomass combined with the same availability of the limiting compound directly reduces the dietary proportion of the limiting compound. Here we tested whether and how interspecific competition in phytoplankton communities leads to changes in resource use efficiency and cellular concentrations of nutrients and fatty acids. The measured particulate carbon : phosphorus ratios (C:P) and fatty acid concentrations in the communities were compared to the theoretically expected ratios and concentrations of measurements on simultaneously running monocultures. With interspecific competition, phytoplankton communities had higher concentrations of the monounsaturated fatty acid oleic acid and also much higher concentrations of the ecologically and physiologically relevant long-chain polyunsaturated fatty acid eicosapentaenoic acid than expected concentrations based on monocultures. Such higher availability of essential fatty acids may contribute to the positive relationship between phytoplankton diversity and zooplankton growth, and may compensate limitations by mineral nutrients in higher trophic levels.}, language = {en} } @article{PiephoArtsWacker2012, author = {Piepho, Maike and Arts, Michael T. and Wacker, Alexander}, title = {Species-specific variation in fatty acid concentrations of four phytoplankton species does phosphorus supply influence the effect of light intensity of temperature?}, series = {Journal of phycology}, volume = {48}, journal = {Journal of phycology}, number = {1}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0022-3646}, doi = {10.1111/j.1529-8817.2011.01103.x}, pages = {64 -- 73}, year = {2012}, abstract = {We tested, in the laboratory, the influence of light intensity, temperature, and phosphorus (P) supply on fatty acid (FA) concentrations of four freshwater algae: the green algae Scenedesmus quadricauda (Turpin) Breb. and Chlamydomonas globosa J. Snow, the cryptophyte Cryptomonas ovata Ehrenb., and the diatom Cyclotella meneghiniana Kutz. We investigated the main and interactive effects of two variables on algal FA concentrations (i.e., light intensity and P supply or temperature and P supply). Interactive effects of light intensity and P supply were most pronounced in C. meneghiniana, but were also found in S. quadricauda and C. ovata. Changes in several saturated and unsaturated FA concentrations with light were more distinct in the low-P treatments than in the high-P treatments. Interactive effects of temperature and P supply on various FA concentrations were observed in all four species, but there was no consistent pattern. In lake ecosystems, P limitation often coincides with high light intensities and temperatures in summer. Therefore, it is important to examine how combinations of these environmental conditions affect FA concentrations of primary producers that are important sources of FAs for higher trophic levels.}, language = {en} }