Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression can be estimated from plasma VLDL fatty acid ratios.
BACKGROUND
Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the limiting step of monounsaturated fatty acid synthesis in humans and is an important player in triglyceride generation. SCD1 has been repeatedly implicated in the pathogenesis of metabolic and inflammatory diseases. Therefore it is of great importance to determine SCD1 activity in human samples. In this study we aimed to evaluate a hepatic SCD1 activity index derived from plasma VLDL triglyceride composition as a tool to estimate hepatic SCD1 expression in humans. Additionally, we further evaluated commonly used fatty acid ratios [elongase, de novo lipogenesis, and Delta5 and Delta6 desaturase] in plasma VLDL and hepatic lipid fractions.


METHODS
Liver biopsies and plasma samples were simultaneously collected from 15 individuals. Plasma VLDL was obtained by ultracentrifugation. Hepatic and plasma VLDL lipids were fractionated by thin-layer chromatography, and the fatty acid composition of each fraction was analyzed by gas chromatography. Hepatic SCD1 expression was determined by real-time PCR.


RESULTS
Hepatic SCD1 mRNA expression was associated with the product/precursor ratios (16:1/16:0 and 18:1/18:0) of hepatic lipid fractions. The 16:1/16:0 ratio in hepatic and VLDL triglycerides as well as the 18:1/18:0 ratio in plasma VLDL were closely associated with hepatic SCD1 expression. The hepatic de novo lipogenesis index from triglycerides was associated with expression of lipogenic genes [fatty acid synthase (FASN), acetyl-Coenzyme A carboxylase alpha (ACACA), and sterol regulatory element binding transcription factor 1 (SREBP-1)] and is closely reflected by the de novo lipogenesis index in VLDL triglycerides.


CONCLUSIONS
We demonstrated for the first time that hepatic SCD1 expression can be estimated noninvasively from routine blood samples by measuring the SCD1 activity index in fasting plasma VLDL.
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen Germany. Andreas.Peter@med.uni-tuebingen.de
Andreas
A
Peter
Alexander
A
Cegan
Silvia
S
Wagner
Rainer
R
Lehmann
Norbert
N
Stefan
Alfred
A
Königsrainer
Ingmar
I
Königsrainer
Hans-Ulrich
HU
Häring
Erwin
E
Schleicher
D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis; D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics; D000368:Aged; D002855:Chromatography, Thin Layer; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000096:biosynthesis / Q000235:genetics; D000081031:Fatty Acid Elongases; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000737:chemistry*; D005260:Female; D006801:Humans; D050602:Linoleoyl-CoA Desaturase / Q000096:biosynthesis / Q000235:genetics; D008055:Lipids / Q000737:chemistry*; D050155:Lipogenesis; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis* / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis; D014280:Triglycerides / Q000097:blood / Q000737:chemistry*
D000090943:Delta-5 Fatty Acid Desaturase; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D044943:Fatty Acid Desaturases; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D050602:Linoleoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase