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Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis.

Abstract：

BACKGROUND:Data from studies in patients with nonalcoholic steatohepatitis (NASH) suggest an increased hepatic fatty acid oxidation. We have previously shown higher fasting plasma bile acid concentrations in patients with NASH. In-vivo and in-vitro studies suggest that bile acids by binding to peroxisome proliferator-activated receptor α activate fibroblast growth factor 21 (FGF21) and increase hepatic fatty acid oxidation. METHODS:Plasma bile acid levels were quantified in healthy controls (n=38) and patients with biopsy-proven NASH (n=36). Plasma concentration of fatty acids, β-hydroxybutyrate, insulin, glucose, leptin, alanine aminotransferase, FGF21, and 8-hydroxydeoxyguanosine, a measure of oxidative stress, were measured in 16 healthy controls and 10 patients with NASH in the fasted state and in response to 3 h of infusion of intralipid. In a subgroup of these patients (n=6 each), plasma ceramide subspecies were quantified. RESULTS:Fasting plasma bile acids, FGF21, and leptin concentrations were significantly higher in patients with NASH. In response to intralipid infusion there was an increase in plasma β-hydroxybutyrate and free fatty acid levels in both controls and NASH; however, the ratio of β-hydroxybutyrate/free fatty acid was higher in NASH (P=0.02). Plasma FGF21 concentration increased in response to intralipid in patients with NASH only (P<0.01). Plasma leptin, insulin, glucose, and alanine transferase concentrations did not change in either group after infusion of intralipid. Increase in total ceramides in response to intralipid was greater in NASH. CONCLUSION:Elevated bile acids and FGF21 may be responsible for the higher hepatic fatty acid oxidation in NASH.

journal_name

Eur J Gastroenterol Hepatol

journal_title

European journal of gastroenterology & hepatology

authors

Dasarathy S,Yang Y,McCullough AJ,Marczewski S,Bennett C,Kalhan SC

doi

10.1097/MEG.0b013e328345c8c7

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

382-8

issue

eissn

0954-691X

issn

1473-5687

journal_volume

pub_type

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Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis.