@article{SchutkowskiKoenigKlugeetal.2019, author = {Schutkowski, Alexandra and K{\"o}nig, Bettina and Kluge, Holger and Hirche, Frank and Henze, Andrea and Schwerdtle, Tanja and Lorkowski, Stefan and Dawczynski, Christine and Gabel, Alexander and Grosse, Ivo and Stangl, Gabriele I.}, title = {Metabolic footprint and intestinal microbial changes in response to dietary proteins in a pig model}, series = {The journal of nutritional biochemistry}, volume = {67}, journal = {The journal of nutritional biochemistry}, publisher = {Elsevier}, address = {New York}, issn = {0955-2863}, doi = {10.1016/j.jnutbio.2019.02.004}, pages = {149 -- 160}, year = {2019}, abstract = {Epidemiological studies revealed that dietary proteins can contribute to the modulation of the cardiovascular disease risk. Still, direct effects of dietary proteins on serum metabolites and other health-modulating factors have not been fully explored. Here, we compared the effects of dietary lupin protein with the effects of beef protein and casein on the serum metabolite profile, cardiovascular risk markers and the fecal microbiome. Pigs were fed diets containing 15\% of the respective proteins for 4 weeks. A classification analysis of the serum metabolites revealed six biomarker sets of two metabolites each that discriminated between the intake of lupin protein, lean beef or casein. These biomarker sets included 1- and 3-methylhistidine, betaine, carnitine, homoarginine and methionine. The study revealed differences in the serum levels of the metabolites 1- and 3- methylhistidine, homoarginine, methionine and homocysteine, which are involved in the one-carbon cycle. However, these changes were not associated with differences in the methylation capacity or the histone methylation pattern. With the exception of serum homocysteine and homoarginine levels, other cardiovascular risk markers, such as the homeostatic model assessment index, trimethylamine-N-oxide and lipids, were not influenced by the dietary protein source. However, the composition of the fecal microorganisms was markedly changed by the dietary protein source. Lupin-protein-fed pigs exhibited more species from the phyla Bacteroidetes and Firmicutes than the other two groups. In conclusion, different dietary protein sources induce distinct serum metabolic fingerprints, have an impact on the cardiovascular risk and modulate the composition of the fecal microbiome. (C) 2019 Elsevier Inc. All rights reserved.}, language = {en} } @inproceedings{EspeRailaHenzeetal.2012, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Blouin, Katja and Schneider, A. and Schmiedeke, D. and Krane, Vera and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients}, series = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, volume = {60}, booktitle = {Annals of nutrition \& metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0250-6807}, pages = {137 -- 137}, year = {2012}, language = {en} } @article{EspeRailaHenzeetal.2013, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Blouin, Katja and Schneider, Andreas and Schmiedeke, Daniel and Krane, Vera and Pilz, Stefan and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Low plasma alpha-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients}, series = {Clinical journal of the American Society of Nephrology}, volume = {8}, journal = {Clinical journal of the American Society of Nephrology}, number = {3}, publisher = {American Society of Nephrology}, address = {Washington}, organization = {German Diabet \& Dialysis Study Inv}, issn = {1555-9041}, doi = {10.2215/CJN.04880511}, pages = {452 -- 458}, year = {2013}, abstract = {Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, \& measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79\% higher risk of stroke and a 31\% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95\% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95\% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.}, language = {en} } @article{FeddersMuenznerWeberetal.2021, author = {Fedders, Ronja and Muenzner, Matthias and Weber, Pamela and Sommerfeld, Manuela and Knauer, Miriam and Kedziora, Sarah and Kast, Naomi and Heidenreich, Steffi and Raila, Jens and Weger, Stefan and Henze, Andrea and Schupp, Michael}, title = {Liver-secreted RBP4 does not impair glucose homeostasis in mice}, series = {The journal of biological chemistry}, volume = {293}, journal = {The journal of biological chemistry}, number = {39}, publisher = {American Society for Biochemistry and Molecular Biology}, address = {Bethesda}, issn = {1083-351X}, doi = {10.1074/jbc.RA118.004294}, pages = {15269 -- 15276}, year = {2021}, abstract = {Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis.}, language = {en} } @article{EspeRailaHenzeetal.2011, author = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Krane, Vera and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane}, title = {Impact of vitamin A on clinical outcomes in haemodialysis patients}, series = {Nephrology, dialysis, transplantation}, volume = {26}, journal = {Nephrology, dialysis, transplantation}, number = {12}, publisher = {Oxford Univ. Press}, address = {Oxford}, organization = {German Diabetes \& Dialysis Study I}, issn = {0931-0509}, doi = {10.1093/ndt/gfr171}, pages = {4054 -- U583}, year = {2011}, abstract = {Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study. Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations. Results. Patients had a mean age of 66 +/- 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) mu mol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 mu mol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 mu mol/L; HR 1.81, 95\% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95\% CI 1.41-3.50) and fatal infection (HR 2.19, 95\% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 mu mol/L) were more likely to die of any cause (HR 1.43, 95\% CI 1.14-1.80), experience SCD (HR 1.97, 95\% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95\% CI 1.10-1.85). Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients.}, language = {en} } @article{HenzeAumerGrabneretal.2011, author = {Henze, Andrea and Aumer, Franziska and Grabner, Arthur and Raila, Jens and Schweigert, Florian J.}, title = {Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling}, series = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, volume = {106}, journal = {The British journal of nutrition : an international journal devoted to the science of human and animal nutrition}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {0007-1145}, doi = {10.1017/S0007114511000845}, pages = {S170 -- S173}, year = {2011}, abstract = {Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.}, language = {en} } @misc{HenzeAumerGrabneretal.2011, author = {Henze, Andrea and Aumer, Franziska and Grabner, Arthur and Raila, Jens and Schweigert, Florian J.}, title = {Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {567}, issn = {1866-8372}, doi = {10.25932/publishup-41288}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-412886}, pages = {4}, year = {2011}, abstract = {Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses.}, language = {en} } @article{FruscalzoFrommerLonderoetal.2017, author = {Fruscalzo, Arrigo and Frommer, Julia-Marie and Londero, Ambrogio P. and Henze, Andrea and Schweigert, Florian J. and Nofer, Jerzy-Roch and Steinhard, Johannes and Klockenbusch, Walter and Schmitz, Ralf and Raila, Jens}, title = {First trimester TTR-RBP4-ROH complex and angiogenic factors in the prediction of small for gestational age infant's outcome}, series = {Archives of gynecology and obstetrics}, volume = {295}, journal = {Archives of gynecology and obstetrics}, publisher = {Springer}, address = {Heidelberg}, issn = {0932-0067}, doi = {10.1007/s00404-017-4338-4}, pages = {1157 -- 1165}, year = {2017}, abstract = {To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight < 10\%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37). We found decreased RBP4 in SGA patients that delivered fetuses < 3\% and in fetuses delivered after the 37 weeks of gestation compared to controls [1.50 (95\% CI 1.40-1.75) vs 1.62 (95\% CI 1.47-1.98), p < 0.05]. Further, we found lower PlGF and sFlt-1 concentrations in SGA that delivered before 37 weeks of gestation compared to controls (respectively, PIGF and sFlt-1: 39.7 pg/ml (95\% CI 32.3-66.3) vs 62.9 pg/ml (95\% CI 45.2-78.4) and 906 pg/ml (95\% CI 727-1626) vs 1610 pg/ml (95\% CI 1088-212), p < 0.05). First trimester maternal serum RBP4 and angiogenic factors PlGF and sFlt-1 can differently predict the timing of delivery of pregnancies complicated by SGA fetuses.}, language = {en} } @article{FruscalzoLonderoDriuletal.2015, author = {Fruscalzo, Arrigo and Londero, Ambrogio P. and Driul, Lorenza and Henze, Andrea and Tonutti, Laura and Ceraudo, Maria and Zanotti, Giuseppe and Berni, Rodolfo and Schweigert, Florian J. and Raila, Jens}, title = {First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus}, series = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine}, volume = {53}, journal = {Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine}, number = {10}, publisher = {De Gruyter}, address = {Berlin}, issn = {1434-6621}, doi = {10.1515/cclm-2014-0929}, pages = {1643 -- 1651}, year = {2015}, abstract = {Background: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy. Methods: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean +/- SD: TTR 3.96 +/- 0.89 mu mol/L vs. 4.68 +/- 1.21 mu mol/L, RBP4 1.13 +/- 0.25 mu mol/L vs. 1.33 +/- 0.38 mu mol/L and ROH 1.33 +/- 0.17 mu mol/L vs. 1.62 +/- 0.29 mu mol/L, p < 0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p < 0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95\% CI 0.87-0.98, p < 0.05). Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.}, language = {en} } @article{FreySprangerHenzeetal.2009, author = {Frey, Simone K. and Spranger, Joachim and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Raila, Jens}, title = {Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus}, issn = {0026-0495}, doi = {10.1016/j.metabol.2009.05.003}, year = {2009}, abstract = {Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.}, language = {en} }