TY - JOUR A1 - von Websky, Karoline A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Reichetzeder, Christoph A1 - Tsuprykov, Oleg A1 - Hocher, Berthold T1 - Impact of vitamin D on pregnancy-related disorders and on offspring outcome JF - The Journal of Steroid Biochemistry and Molecular Biology N2 - Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation. During pregnancy, adaptations in maternal vitamin D metabolism lead to a physiologic increase of vitamin D levels, mainly because of an increased renal production, although other potential sources like the placenta are being discussed. A sufficient supply of mother and child with calcium and vitamin D during pregnancy ensures a healthy bone development of the fetus, whereas lack of either of these nutrients can lead to the development of rickets in the child. Moreover, vitamin D insufficiency during pregnancy has consistently been associated with adverse maternal and neonatal pregnancy outcomes. In multitudinous studies, low maternal vitamin D status was associated with a higher risk for pre-eclampsia, gestational diabetes mellitus and other gestational diseases. Likewise, several negative consequences for the fetus have been reported, including fetal growth restriction, increased risk of preterm birth and a changed susceptibility for later-life diseases. However, study results are diverging and causality has not been proven so far. Meta-analyses on the relationship between maternal vitamin D status and pregnancy outcomes revealed a wide heterogeneity of studied populations and the applied methodology in vitamin D assessment. Until today, clinical guidelines for supplementation cannot be based on high-quality evidence and it is not clear if the required intake for pregnant women differs from non-pregnant women. Long-term safety data of vitamin D supplementation in pregnant women has not been established and overdosing of vitamin D might have unfavorable effects, especially in mothers and newborns with mutations of genes involved in vitamin D metabolism. Reliable data from large observational and interventional randomized control trials are urgently needed as a basis for any detailed and safe recommendations for supplementation in the general population and, most importantly, in pregnant women. This is of utmost importance, as ensuring a sufficient vitamin D-supply of mother and child implies a great potential for the prevention of birth complications and development of diseases. KW - Vitamin D deficiency KW - Free vitamin D KW - Vitamin D binding protein KW - Epigenetics KW - DNA methylation KW - Single nucleotide polymorphism KW - Preeclampsia KW - Gestational diabetes mellitus KW - Small for gestational age KW - Long term health Y1 - 2018 U6 - https://doi.org/10.1016/j.jsbmb.2017.11.008 SN - 0960-0760 VL - 180 SP - 51 EP - 64 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Li, Jian A1 - Lu, Yong-Ping A1 - Tsuprykov, Oleg A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Reichetzeder, Christoph A1 - Tian, Mei A1 - Zhang, Xiao Li A1 - Zhang, Qin A1 - Sun, Guo-Ying A1 - Guo, Jingli A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Peng, Xiao-Ning A1 - Lin, Ge A1 - Hocher, Berthold T1 - Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Methods Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy. KW - Glucose tolerance KW - High-fat-sucrose-salt diet KW - Maternal folate treatment KW - Paternal programming Y1 - 2018 U6 - https://doi.org/10.1007/s00125-018-4635-x SN - 0012-186X SN - 1432-0428 VL - 61 IS - 8 SP - 1862 EP - 1876 PB - Springer CY - New York ER - TY - JOUR A1 - Glosse, Philipp A1 - Feger, Martina A1 - Mutig, Kerim A1 - Chen, Hong A1 - Hirche, Frank A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Hocher, Berthold A1 - Lang, Florian A1 - Föller, Michael T1 - AMP-activated kinase is a regulator of fibroblast growth factor 23 production JF - Kidney international : official journal of the International Society of Nephrology N2 - Fibroblast growth factor 23 (FGF23) is a proteohormone regulating renal phosphate transport and vitamin D metabolism as well as inducing left heart hypertrophy. FGF23-deficient mice suffer from severe tissue calcification, accelerated aging and a myriad of aging-associated diseases. Bone cells produce FGF23 upon store-operated calcium ion entry (SOCE) through the calcium selective ion channel Orai1. AMP-activated kinase (AMPK) is a powerful energy sensor helping cells survive states of energy deficiency, and AMPK down-regulates Orai1. Here we investigated the role of AMPK in FGF23 production. Fgf23 gene transcription was analyzed by qRT-PCR and SOCE by fluorescence optics in UMR106 osteoblast-like cells while the serum FGF23 concentration and phosphate metabolism were assessed in AMPKa1-knockout and wild-type mice. The AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) down-regulated, whereas the AMPK inhibitor, dorsomorphin dihydrochloride (compound C) and AMPK gene silencing induced Fgf23 transcription. AICAR decreased membrane abundance of Orai1 and SOCE. SOCE inhibitors lowered Fgf23 gene expression induced by AMPK inhibition. AMPKa1-knockout mice had a higher serum FGF23 concentration compared to wild-type mice. Thus, AMPK participates in the regulation of FGF23 production in vitro and in vivo. The inhibitory effect of AMPK on FGF23 production is at least in part mediated by Orai1-involving SOCE. KW - calcium KW - FGF23 KW - Klotho KW - Orai1 KW - phosphate KW - parathyroid hormone Y1 - 2018 U6 - https://doi.org/10.1016/j.kint.2018.03.006 SN - 0085-2538 SN - 1523-1755 VL - 94 IS - 3 SP - 491 EP - 501 PB - Elsevier CY - New York ER - TY - THES A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed T1 - GLP-1 receptor-independent mechanisms of DPP-4 inhibition on renal disease progression T2 - GLP-1 Rezeptor-unabhängige Mechanismen von DPP-4 Hemmung bei der Fortschreitung der Nierenerkrankung Y1 - 2018 ER -