Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity

• Published in: Metabolism, clinical and experimental clinical and experimental, 2016-05, Vol.65 (5), p.655-666
• Main Authors: Walle, Paula, Takkunen, Markus, Männistö, Ville, Vaittinen, Maija, Lankinen, Maria, Kärjä, Vesa, Käkelä, Pirjo, Ågren, Jyrki, Tiainen, Mika, Schwab, Ursula, Kuusisto, Johanna, Laakso, Markku, Pihlajamäki, Jussi
• Format: Article
• Language: English
• Subjects: Adult; Body Mass Index; Cholesterol Esters - blood; Cholesterol Esters - metabolism; Cohort Studies; Cross-Sectional Studies; Endocrinology & Metabolism; Fatty acid desaturase; Fatty Acid Desaturases - genetics; Fatty Acid Desaturases - metabolism; Fatty Acids - blood; Fatty Acids - metabolism; Fatty Liver - complications; Fatty Liver - epidemiology; Fatty Liver - metabolism; Fatty Liver - pathology; Female; Finland - epidemiology; Gastric Bypass; Gene Expression Regulation, Enzymologic; Hepatic mRNA expression; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Liver - enzymology; Liver - metabolism; Liver - pathology; Liver fatty acid composition; Male; Metabolic Syndrome - complications; Metabolic Syndrome - epidemiology; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Middle Aged; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - epidemiology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - pathology; Obesity, Morbid - complications; Obesity, Morbid - surgery; Risk; Serum fatty acid composition; Triglycerides - blood; Triglycerides - metabolism
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2016.01.011

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 ± 9.5 years (mean ± SD), BMI 44.2 ± 6.2 kg/m2 ). 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.