Hepatic Stearoyl-CoA Desaturase (SCD)-1 Activity and Diacylglycerol but Not Ceramide Concentrations Are Increased in the Nonalcoholic Human Fatty Liver

Hepatic Stearoyl-CoA Desaturase (SCD)-1 Activity and Diacylglycerol but Not Ceramide Concentrations Are Increased in the Nonalcoholic Human Fatty Liver Anna Kotronen 1 2 , Tuulikki Seppänen-Laakso 3 , Jukka Westerbacka 1 , Tuula Kiviluoto 4 , Johanna Arola 5 , Anna-Liisa Ruskeepää 3 , Matej Orešič 3 and Hannele Yki-Järvinen 1 1 Department of Medicine, Division of Diabetes, Helsinki, Finland 2 Minerva Medical Research Institute, Helsinki, Finland 3 VTT Technical Research Centre of Finland, Espoo, Finland 4 Department of Surgery, University of Helsinki, Helsinki, Finland 5 Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland Corresponding author: Anna Kotronen, anna.kotronen{at}helsinki.fi Abstract OBJECTIVE— To determine whether 1 ) hepatic ceramide and diacylglycerol concentrations, 2 ) SCD1 activity, and 3 ) hepatic lipogenic index are increased in the human nonalcoholic fatty liver. RESEARCH DESIGN AND METHODS— We studied 16 subjects with ( n = 8) and without ( n = 8) histologically determined nonalcoholic fatty liver (NAFL + and NAFL − ) matched for age, sex, and BMI. Hepatic concentrations of lipids and fatty acids were quantitated using ultra-performance liquid chromatography coupled to mass spectrometry and gas chromatography. RESULTS— The absolute (nmol/mg) hepatic concentrations of diacylglycerols but not ceramides were increased in the NAFL + group compared with the NAFL − group. The livers of the NAFL + group contained proportionally less long-chain polyunsaturated fatty acids as compared with the NAFL − group. Liver fat percent was positively related to hepatic stearoyl-CoA desaturase 1 (SCD1) activity index ( r = 0.70, P = 0.003) and the hepatic lipogenic index ( r = 0.54, P = 0.030). Hepatic SCD1 activity index was positively related to the concentrations of diacylglycerols ( r = 0.71, P = 0.002) but not ceramides ( r = 0.07, NS). CONCLUSIONS— We conclude that diacylglycerols but not ceramides are increased in NAFL. The human fatty liver is also characterized by depletion of long polyunsaturated fatty acids in the liver and increases in hepatic SCD1 and lipogenic activities. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 24 October 2008. M.O. and H.Y.-J. share senior authorship of this study. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for d