title: Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity.
abstract: BACKGROUND
  Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown.
  
  
  METHODS
  Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease.
  
  
  RESULTS
  Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, p<0.002) and stearoyl-CoA desaturase 1 (SCD1, p<0.002) and lower activity of delta-5 desaturase (D5D, p<0.002) when compared to individuals with normal liver. Estimated activities of D5D, D6D and SCD1 correlated positively between liver and serum indicating that serum estimates reflected liver metabolism. Accordingly, NASH was associated with higher hepatic mRNA expression of corresponding genes FADS1, FADS2 and SCD. Finally, differences in FA metabolism that associated with NASH in obese individuals were also associated with high ALT in the METSIM Study.
  
  
  CONCLUSIONS
  We demonstrated alterations in FA metabolism and endogenous desaturase activities that associate with NASH, independent of obesity and diet. This suggests that changes in endogenous FA metabolism are related to NASH and that they may contribute to the progression of the disease.
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Walle
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Takkunen
authors.affiliation: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Männistö
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Vaittinen
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Lankinen
authors.affiliation: Department of Pathology, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.affiliation: Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Käkelä
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Finland.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Ågren
authors.affiliation: School of Pharmacy, University of Eastern Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland; Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schwab
authors.affiliation: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.affiliation: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland; Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland. Electronic address: jussi.pihlajamaki@uef.fi.
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005234:Fatty Liver / Q000150:complications / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005387:Finland / Q000453:epidemiology; D015390:Gastric Bypass; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D009767:Obesity, Morbid / Q000150:complications* / Q000601:surgery; D012306:Risk; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D000090943:Delta-5 Fatty Acid Desaturase; D005227:Fatty Acids; D007527:Isoenzymes; D014280:Triglycerides; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human
keywords: Fatty acid desaturase; Hepatic mRNA expression; Liver fatty acid composition; Non-alcoholic fatty liver disease; Serum fatty acid composition