title: 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.
  
  
  CONCLUSIONS
  Elevated bile acids and FGF21 may be responsible for the higher hepatic fatty acid oxidation in NASH.
authors: Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA. dasaras@ccf.org
authors: Srinivasan
authors: S
authors: Dasarathy
authors: Yu
authors: Y
authors: Yang
authors: Arthur J
authors: AJ
authors: McCullough
authors: Susan
authors: S
authors: Marczewski
authors: Carole
authors: C
authors: Bennett
authors: Satish C
authors: SC
authors: Kalhan
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002518:Ceramides / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004655:Emulsions / Q000008:administration & dosage; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010743:Phospholipids / Q000008:administration & dosage; D013024:Soybean Oil / Q000008:administration & dosage
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D002518:Ceramides; D004655:Emulsions; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin; D010743:Phospholipids; C414620:fibroblast growth factor 21; C545823:soybean oil, phospholipid emulsion; D005346:Fibroblast Growth Factors; D013024:Soybean Oil; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase; D003849:Deoxyguanosine; D020155:3-Hydroxybutyric Acid