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Your search keyword '"AK Schilling"' showing total 2 results
Start Over Author "AK Schilling" Topic fatty liver
2 results on '"AK Schilling"'

1. Intestinal vitamin D receptor modulates lipid metabolism, adipose tissue inflammation and liver steatosis in obese mice.

Author

Jahn D, Dorbath D, Schilling AK, Gildein L, Meier C, Vuille-Dit-Bille RN, Schmitt J, Kraus D, Fleet JC, Hermanns HM, and Geier A

Subjects
Adipose Tissue metabolism, Adipose Tissue pathology, Adult, Aged, Angiopoietin-Like Protein 4 metabolism, Animals, Cohort Studies, Fatty Liver metabolism, Fatty Liver pathology, Female, Gene Expression Regulation, Humans, Inflammation, Intestinal Mucosa pathology, Lipid Metabolism genetics, Lipoprotein Lipase antagonists & inhibitors, Lipoprotein Lipase metabolism, Liver pathology, Male, Mice, Mice, Obese, Mice, Transgenic, Middle Aged, Receptors, Calcitriol deficiency, Signal Transduction, Transcription, Genetic, Transgenes, Triglycerides metabolism, Angiopoietin-Like Protein 4 genetics, Fatty Liver genetics, Intestinal Mucosa metabolism, Lipoprotein Lipase genetics, Liver metabolism, Receptors, Calcitriol genetics
Abstract

Objective: Hypovitaminosis D is common in the obese population and patients suffering from obesity-associated disorders such as type 2 diabetes and fatty liver disease, resulting in suggestions for vitamin D supplementation as a potential therapeutic option. However, the pathomechanistic contribution of the vitamin D-vitamin D receptor (VDR) axis to metabolic disorders is largely unknown., Methods: We analyzed the pathophysiological role of global and intestinal VDR signaling in diet-induced obesity (DIO) using global Vdr-/- mice and mice re-expressing an intestine-specific human VDR transgene in the Vdr deficient background (Vdr-/- hTg)., Results: Vdr-/- mice were protected from DIO, hepatosteatosis and metabolic inflammation in adipose tissue and liver. Furthermore, Vdr-/- mice displayed a decreased adipose tissue lipoprotein lipase (LPL) activity and a reduced capacity to harvest triglycerides from the circulation. Intriguingly, all these phenotypes were partially reversed in Vdr-/- hTg animals. This clearly suggested an intestine-based VDR activity on systemic lipid homeostasis. Scrutinizing this hypothesis, we identified the potent LPL inhibitor angiopoietin-like 4 (Angptl4) as a novel transcriptional target of VDR., Conclusion: Our study suggests a VDR-mediated metabolic cross-talk between gut and adipose tissue, which significantly contributes to systemic lipid homeostasis. These results have important implications for use of the intestinal VDR as a therapeutic target for obesity and associated disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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2. Increased frequencies of activated effector CD4+ T cells in the peripheral blood and hepatic tissue of patients with NAFL and NASH

Author

C Jurowich, AK Schilling, Niklas Beyersdorf, T Kudlich, I Hering, J Meertens, Monika Rau, and Andreas Geier

Subjects
medicine.medical_treatment, Fatty liver, Gastroenterology, Inflammation, Biology, medicine.disease, Peripheral blood mononuclear cell, digestive system diseases, Cytokine, Immune system, Immunology, medicine, IL-2 receptor, medicine.symptom, Steatohepatitis, Interleukin 4
Abstract

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges between 20 – 35% in Europe. In 5 to 20% there is a progression from non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) but it is still not understood why some people develop NASH. The current hypothesis about the pathogenesis is a two hit theory. The “first hit” causes a steatosis and the “second hit” in form of bacterial translocation leads to an inflammation and the development of NASH. Hepatic Th17 cell infiltration was observed in a NASH mouse model and higher IL-17 and IL-21 gene expression in human liver of NASH patients. We hypothesized that the phenotype of peripheral CD4+ T cells might be predictive for the degree and quality of hepatic T cell infiltration and histopathology. Aims: Characterization of CD4+ regulatory T cells (Tregs) and conventional CD4+ T cells in peripheral blood and hepatic tissue in patients with NAFL and NASH. Methods: 50 patients with histology-proven NAFL or NASH and 44 healthy controls (HC) were included in this study. PBMCs of peripheral blood and hepatic tissue were characterized by multi-colour FACS analysis. CD4+ T cells were stimulated with PMA and ionomycin for intracellular detection of cytokine production (IL-17, IL-4, INF-g, IL-21). Results: Patients were older and had a higher BMI in comparison to HC. In patients with NAFL and NASH a lower frequency of resting Tregs (CD4+CD45RA+CD25++) was observed in peripheral blood. We found changes in effector CD4+ T cells with higher frequencies of IFN-g+, IL-21+ and IL4+ cells among CD4+ T cells of the peripheral blood of patients. In hepatic tissue, higher frequency of IL17+, IFN-g+, IL21+ and IL4+ cells were measured among CD4+ T cells than in the peripheral blood. CD4+ T cells in peripheral blood and hepatic tissue contained higher frequencies of HLA-DR+, i.e. activated cells. Conclusions: The peripheral blood and hepatic tissue of patients with NAFLD contained higher frequencies of activated effector cells among CD4+ T cells. NAFL patients show a “prehepatitic” immune cell profile very similar to that seen in NASH. Our data suggest that interfering with the effector CD4+ T cell response might prevent progression from NAFL to NASH.

Published
2014
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