Publications

Carsten Carlberg

Genomic signaling of vitamin D

Steroids, Volume 196, August 2023

It took several hundred million years of evolution, in order to develop the endocrine vitamin D signaling system, which is formed by a nuclear receptor, the transcription factor VDR (vitamin D receptor), its ligand, the vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and several metabolizing enzymes and transport proteins. Even within the nuclear receptor superfamily the affinity of VDR for 1,25(OH)2D3 is outstandingly high (KD = 0.1 nM). The activation of VDR by 1,25(OH)2D3 is the core mechanism of genomic signaling of vitamin D3, which results in the modulation of the epigenome at thousands of promoter and enhancer regions as well as finally in the activation or repression of hundreds of target gene transcription. In addition, rapid non-genomic actions of vitamin D are described, which are mechanistically far less understood. The main function of vitamin D is to keep the human body in homeostasis. This implies the control of calcium levels, which is essential for bone mineralization, as well as for pushing of innate immunity to react sufficiently strong to microbe infection and preventing overreactions of adaptive immunity, i.e., not to cause autoimmune diseases. This review will discuss whether genomic signaling is sufficient for explaining all physiological functions of vitamin D3.

https://doi.org/10.1016/j.steroids.2023.109271

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Carsten Carlberg, Eunike Velleuer

Nutrition and epigenetic programming

Current Opinion in Clinical Nutrition and Metabolic Care, 26(3), May 2023

Chromatin is the physical expression of the epigenome and has a memory function on the level of DNA methylation, histone modification and 3-dimensional (3D) organization. This epigenetic memory does not only affect transient gene expression but also represents long-lasting decisions on cellular fate. The memory is based on an epigenetic programming process, which is directed by extracellular and intracellular signals that are sensed by transcription factors and chromatin modifiers. Many dietary molecules and their intermediary metabolites serve as such signals, that is they contribute to epigenetic programming and memory. In this context, we will discuss about molecules of intermediary energy metabolism affecting chromatin modifier actions, nutrition-triggered epigenetic memory in pre- and postnatal phases of life; and epigenetic programming of immune cells by vitamin D. These mechanisms explain some of the susceptibility for complex diseases, such as the metabolic syndrome, cancer and immune disorders.

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Carsten Carlberg, Marianna Raczyk, Natalia Zawrotna

Vitamin D: A master example of nutrigenomics

Redox Biology, Volume 62, 2023

Nutrigenomics attempts to characterize and integrate the relation between dietary molecules and gene expression on a genome-wide level. One of the biologically active nutritional compounds is vitamin D3, which activates via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) the nuclear receptor VDR (vitamin D receptor). Vitamin D3 can be synthesized endogenously in our skin, but since we spend long times indoors and often live at higher latitudes where for many winter months UV-B radiation is too low, it became a true vitamin. The ligand-inducible transcription factor VDR is expressed in the majority of human tissues and cell types, where it modulates the epigenome at thousands of genomic sites. In a tissue-specific fashion this results in the up- and downregulation of primary vitamin D target genes, some of which are involved in attenuating oxidative stress. Vitamin D affects a wide range of physiological functions including the control of metabolism, bone formation and immunity. In this review, we will discuss how the epigenome- and transcriptome-wide effects of 1,25(OH)2D3 and its receptor VDR serve as a master example in nutrigenomics. In this context, we will outline the basis of a mechanistic understanding for personalized nutrition with vitamin D3.

https://doi.org/10.1016/j.redox.2023.102695

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Marcus Schmidt & Marianna Raczyk​​

FODMAP reduction strategies for nutritionally valuable baking products: current state and future challenges

Critical Reviews in Food Science and Nutrition

Fermentable oligo-, di- and monosaccharides and polyols (FODMAP) comprise several previously unrelated carbohydrates, such as fructans, fructo-oligosaccharides, galacto-oligosaccharides, fructose (in excess of glucose), mannitol and sorbitol, and among others. For many patients with gastro-intestinal disorders, such as irritable bowel syndrome, the ingestion of FODMAP triggers symptoms and causes discomfort. Among the main contributors to the dietary FODMAP intake are baking products, in particular bread as a major global staple food. This is primarily due to the fructan content of the cereal flours, but also process induced accumulation of FODMAP is possible. To provide low-FODMAP baking products, researchers have investigated various approaches, such as bio-process reduction by yeast, lactic acid bacteria, germination of the raw material or the use of exogenous enzymes. In addition, the selection of appropriate ingredients, which are either naturally or after pretreatment suitable for low-FODMAP products, is discussed. The sensory and nutritional quality of low-FODMAP baking products is another issue, that is addressed, with particular focus on providing sufficient dietary fiber intake. Based on this information, the current state of low-FODMAP baking and future research necessities, to establish practical strategies for low-FODMAP products, are evaluated in this article.

https://doi.org/10.1080/10408398.2023.2195026 

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