Abstract
BackgroundNon-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.MethodsFor 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.ResultsBMI 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.ConclusionsReduced 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 registrationWe 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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients
The term NAFLD is used for a wide spectrum of fatty liver diseases that starts with simple steatosis in non-alcoholic fatty liver (NAFL) that may progress to non-alcoholic steatohepatits (NASH), which is complicated by fibrosis, cirrhosis, and eventually hepatocellular carcinoma [5,6,7]
Fasting Fibroblast growth factor 19 (FGF19) serum concentrations were lowest in obese NAFLD patients and highest in normal-weight healthy controls
Summary
Non-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. 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). Obesity and fatty liver disease represent increasing medical problems in developed countries. Obesity is an important risk factor of non-alcoholic fatty liver disease (NAFLD), which has been reported in 30 to 40% of adults [3, 4]. NAFLD is common in obesity and in overweight patients [9, 10]. Several metabolic factors have already been identified in the development of NAFLD, including insulin resistance, diabetes mellitus and obesity
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