Paula Walle1, Markus Takkunen1, Ville Männistö2, Maija Vaittinen1, Maria Lankinen1, Vesa Kärjä3, Pirjo Käkelä4, Jyrki Ågren5, Mika Tiainen6, Ursula Schwab7, Johanna Kuusisto2, Markku Laakso2, Jussi Pihlajamäki8. 1. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland. 2. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Finland. 3. Department of Pathology, University of Eastern Finland and Kuopio University Hospital, Finland. 4. Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Finland. 5. Institute of Biomedicine, University of Eastern Finland, Finland. 6. School of Pharmacy, University of Eastern Finland. 7. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland; Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland. 8. 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.
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.
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 obeseparticipants 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: Ludovico Abenavoli; Natasa Milic; Laura Di Renzo; Tomislav Preveden; Milica Medić-Stojanoska; Antonino De Lorenzo Journal: World J Gastroenterol Date: 2016-08-21 Impact factor: 5.742