Impaired FGF–19 release and hepatic FGF–19 resistance in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD)

Aims: FGF–19, a novel intestinal hormone, is secreted in the terminal ileum postprandially in response to bile salts. NAFLD is common in obesity, but the molecular mechanisms of NAFLD in non-obese patients remain yet to be defined. FGF–19 could possibly play a beneficial role in NAFLD. The aim of our study was to compare FGF–19 serum concentrations and hepatic response to this enterokine in overweight and obese NAFLD patients as well as healthy volunteers after an oral fat challenge. Patients and methods: In total, we recruited 14 overweight NAFLD patients, 12 obese NAFLD individuals, and 16 healthy controls. NAFLD was diagnosed by ultrasound and/or liver biopsy. Serum FGF–19 levels were determined by ELISA after 10 hrs of overnight fasting. Subsequently, all individuals received 1g fat (Calogen®) per kg body weight orally, and FGF–19 concentrations were measured after 2, 4 and 6 hrs. Serum concentrations of C4, a valid marker of bile acid biosynthesis, were determined by HPLC. Results: Basal FGF–19 levels are significantly lower in obese NAFLD patients as compared to healthy volunteers. The increase of FGF–19 levels in the novel "oral fat tolerance test" (OFTT) differs significantly between controls, overweight and obese NAFLD patients. Of note, overweight NAFLD patients display the lowest FGF–19 levels at all postprandial time points and significantly lower FGF–19 concentrations after 2 hrs in comparison to controls. At all points in time, serum C4 levels are markedly lower in healthy volunteers in comparison to overweight and obese NAFLD patients. Whereas FGF–19 and C4 levels are inversely correlated in controls, C4 concentrations in overweight and obese NAFLD patients remain unchanged for 4 hrs postprandially in spite of increased FGF–19 levels. Conclusions: We have established a protocol for an oral fat tolerance test (OFTT), which demonstrates impaired FGF–19 release and hepatic "FGF–19 resistance" in both overweight and obese NAFLD patients.

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FGF-19 resistance - NAFLD - obesity - overweight