Gewählte Publikation:
Grande, P.
Fibroblast Growth Factor 21 in connection to alcohol consumption and alcoholic liver cirrhosis
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2018. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Horvath Angela
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Stadlbauer-Köllner Vanessa
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- Abstract:
- Introduction: FGF21 is a hepatokine regulating nutritional intake, especially of simple sugars. Its endocrine function relies on FGF-receptors and ßKlotho, which are both present in the hypothalamus and liver. In addition, sugar and alcohol intake enhances the synthesis of FGF21 and highly increased levels of FGF21 decrease the alcohol intake in mice. Therefore, FGF21 might facilitate a liver-brain endocrine axis, by which liver tissue can decrease harmful alcohol intake. The aim of this study was to measure FGF21 levels in patients with alcoholic liver cirrhosis (ALC) and correlate them with their present alcohol consumption. Furthermore, a comparison of these results with non-alcoholic liver cirrhosis (NALC) and healthy test persons was made.
Methods: Detailed information about eating and drinking behaviour of our cohort (ALC: n=41; NALC n=34; Healthy: n=21) was acquired by a food frequency questionnaire. Declared alcohol intake was verified by urine ethyl glucuronide (ETG) levels. FGF21 plasma levels were determined by ELISA. In addition, a cell culture model with human carcinoma hepatocytes was used to test their FGF21 expression in response to alcohol and glucose.
Results: Patients with positive ETG levels (=0.5 µg/ml; equivalent to positive alcohol consumption in the last 12 to 72 hours) showed significantly higher FGF21 plasma levels in comparison to patients with negative ETG levels. This applied to patients with ALC and NALC. The results did not show statistical significance in FGF21 plasma levels according to eating behaviour. The incubation of human hepatocytes with alcohol and glucose did not result in an increase of FGF21 synthesis.
Discussion: Increased FGF21 levels in patients with recent alcohol consumption (verified by ETG) confirmed the first part of the liver-brain endocrine axis: Alcohol consumption seemed to enhance FGF21 synthesis. However, the second part of the liver-brain endocrine axis, a reduction of alcohol intake in case of increased FGF21 levels was not observed. That points towards a pathology in this pathway, which might be caused by a malfunction of ßKlotho or FGF-receptors according to other studies. Further research is required to clarify these pathologies, which may open new pharmacological treatment for patients with alcohol use disorder and alcohol dependence.