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. 2009 Jan;58(1):203-8.
doi: 10.2337/db08-1074. Epub 2008 Oct 24.

Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver

Anna Kotronen  1 , Tuulikki Seppänen-Laakso, Jukka Westerbacka, Tuula Kiviluoto, Johanna Arola, Anna-Liisa Ruskeepää, Matej Oresic, Hannele Yki-Järvinen
Affiliations

Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver

Anna Kotronen et al. Diabetes. 2009 Jan.

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.

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Figures

FIG. 1.
FIG. 1.
Correlation coefficients between each of the 136 individual TG (expressed relative to total hepatic TG) and histological liver fat contents were calculated. These correlation coefficients (Spearman's ρ) were then plotted against the number of double bonds in the respective TGs. An inverse relationship was observed, implying that the TGs that were positively associated with liver fat content had only a few double bonds, whereas those TGs negatively related to liver fat content had many double bonds. r = −0.57; P < 0.0001.
FIG. 2.
FIG. 2.
The relationships between liver fat content and hepatic SCD1 activity index (A), hepatic elongase activity index (B), and hepatic lipogenic index (C).
FIG. 3.
FIG. 3.
The relationships between liver fat content and the hepatic concentrations of diacylglycerols (DG) (A) and ceramides (B).
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