841 CIRCULATING LEVELS OF TNF-LIKE CYTOKINE 1A (TL1A) AND ITS DECOY RECEPTOR 3 (DCR3) IN NASH: MARKERS OF ADVANCED DISEASE

Abstract

Background: FGF-19, a novel intestinal hormone, is secreted in the terminal ileum postprandially and during bile salt absorption. Non-alcoholic fatty liver disease (NAFLD) is common in obesity but the molecular mechanisms of NAFLD development in non-obese patients remain yet to be defined. FGF-19 might play a protective role in NAFLD by improving insulin sensitivity, increasing hepatic beta-oxidation and inhibiting lipogenesis. The aim of our study was to investigate FGF-19 serum concentrations in non-obese (BMI 30kg/m) patients and healthy volunteers in a fasted state and after a defined oral fat load. Patients and Methods: In total, 14 NAFLD patients (mean BMI 27.7 kg/m), 21 obese individuals and 16 healthy controls were recruited. FGF-19 levels were determined by ELISA after 10 hours of overnight fasting. Subsequently, all individuals received 1 g fat (Calogen) per kg body weight orally. FGF-19 serum concentrations were measured at baseline and after 2, 4 and 6 hours. No other food intake was permitted during this time but water was allowed ad libitum. Results: Basal serum FGF-19 levels in the fasted state do not differ between overweight NAFLD patients, obese subjects and normal controls. The oral fat load increases FGF-19 levels in all three groups. FGF-19 serum levels peak after 4 hours in all three groups and were highest in controls (378.9±202.1 pg/ml). In comparison to men, women display significantly higher FGF-19 levels after 6 hours (283.4±189.6 vs. 172.1±82.1 pg/ml, p < 0.05). Of note, non-obese NAFLD patients display the lowest FGF-19 levels at all time points. In particular, FGF-19 levels 2 hours post oral fat load are significantly lower (p = 0.004) in overweight NAFLD patients (143.7±61.4 pg/ml) as compared to both healthy volunteers and obese patients (287.4±177.7 pg/ml and 281.4±235.0 pg/ml respectively). Conclusions: We established an oral fat load test (“OFLT”), which demonstrated impaired FGF-19 release in non-obese NAFLD patients. The hepatic mechanisms consequences of impaired FGF-19 signaling require further investigation.