ABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. Fibroblast growth factor 19 (FGF19), an intestinal hormone, could play a role in the complex pathogenesis of NAFLD. The aim of our study was to investigate responses of FGF19 and bile acid (BA) synthesis after a body weight-adjusted oral fat tolerance test (OFTT) in overweight and obese NAFLD patients. METHODS: For this study, we recruited 26 NAFLD patients; 14 overweight (median BMI 28.3 kg/m2), 12 obese (35.3 kg/m2) and 16 healthy controls (24.2 kg/m2). All individuals received 1 g fat (Calogen®) per kg body weight orally. Serum concentrations of FGF19 were determined by ELISA. Concentrations of BAs and BA synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively; all at 0 (baseline), 2, 4 and 6 h during the OFTT. RESULTS: BMI correlated negatively with fasting FGF19 concentrations (rho = - 0.439, p = 0.004). FGF19 levels of obese NAFLD patients were significantly (p = 0.01) lower in the fasting state (median 116.0 vs. 178.5 pg/ml), whereas overweight NAFLD patients had significantly (p = 0.004) lower FGF19 concentrations 2 h after the fat load (median 163.0 vs. 244.5 pg/ml), and lowest values at all postprandial time points as compared to controls. Baseline BA concentrations correlated positively with FGF19 values (rho = 0.306, p = 0.048). In all groups, we observed BA increases during the OFTT with a peak at 2 h but no change in C4 levels in overweight/obese NAFLD patients. CONCLUSIONS: Reduced basal gastrointestinal FGF19 secretion and decreased postprandial response to oral fat together with blunted effect on BA synthesis indicate alterations in intestinal or hepatic FXR signaling in overweight and obese NAFLD subjects. The precise mechanism of FGF19 signaling after oral fat load needs further evaluation. TRIAL REGISTRATION: We have registered the trial retrospectively on 30 Jan 2018 at the German clinical trials register ( http://www.drks.de /), and the following number has been assigned DRKS00013942 .
Subject(s)
Bile Acids and Salts/biosynthesis , Dietary Fats/administration & dosage , Fibroblast Growth Factors/blood , Liver/metabolism , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/complications , Overweight/complications , Adult , Bile Acids and Salts/blood , Body Mass Index , Cholestenones/blood , Fasting , Female , Fibroblast Growth Factors/metabolism , Humans , Intestinal Mucosa/metabolism , Male , Middle Aged , Obesity/blood , Overweight/blood , Pilot Projects , Young AdultABSTRACT
BACKGROUND: Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. METHODS: This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). RESULTS: The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach's Alpha between .77 and .92), and for all subscales (Cronbach's Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p < .01) and the anxiety (r = .42; p < .01) and depression scales (r = .43; p < .01) of the HADS-D. CONCLUSION: The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies.
