LINICAL ADVANCES IN LIVER , PANCREAS , ND BILIARY TRACT ncreased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty iver Disease

fi K l p ACKGROUND & AIMS: Fibroblast growth factor 21 FGF21) is an hepatic protein that plays a critical role in etabolism, stimulating fatty acid oxidation in liver and lucose uptake in fat. Systemic administration to obese odents and diabetic monkeys leads to improved glucose omeostasis and weight loss. In rodents, FGF21 increases ith fasting and consumption of a ketogenic diet (KD). n humans, FGF21 correlates with body mass index BMI), but studies evaluating other parameters show inonsistent results. We examined FGF21 serum levels in ean and obese individuals and in response to dietary anipulation. We also evaluated FGF21 serum levels and iver messenger RNA (mRNA) expression in nonalcoholic atty liver disease (NAFLD) and nonalcoholic steatohepaitis (NASH). METHODS: Serum FGF21 was measured fter an overnight fast in individuals with BMI ranging rom normal to obese. Volunteers fasted for 16 or 72 ours and then ate a standard meal. Another group onsumed KD for 12 days. Serum FGF21 and hepatic RNA expression were measured in obese individuals ith NAFLD or NASH. RESULTS: There was a positive orrelation between BMI and FGF21. There was no hange in FGF21 in response to a short fast or KD. A onstatistically significant fall in FGF21 levels was seen fter a 72-hour fast. Hepatic FGF21 mRNA expression as significantly elevated in NAFLD, which correlated ith a substantial increase in serum FGF21. In NASH, erum FGF21 but not liver mRNA was increased. CONLUSIONS: FGF21 correlates with BMI and may be a ovel biomarker for NAFLD, but is not nutritionally egulated in humans.