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Diabetologia
Published in: Diabetologia 4/2008

01-04-2008 | Article

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans

Authors: N. Stefan, A. Peter, A. Cegan, H. Staiger, J. Machann, F. Schick, C. D. Claussen, A. Fritsche, H.-U. Häring, E. Schleicher

Published in: Diabetologia | Issue 4/2008

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Abstract

Aims/hypothesis

Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. It is imperative for the assembly of VLDL particles, which transport triacylglycerol (TG) from liver to adipose tissue and other sites. We aimed to determine the role of hepatic SCD1 activity in human glucose and lipid metabolism.

Methods

We studied 54 people participating in a lifestyle intervention programme with diet modification and increased physical activity. Insulin sensitivity was determined during a euglycaemic–hyperinsulinaemic clamp and estimated from an OGTT. Liver fat was quantified by 1H-magnetic resonance spectroscopy at baseline and after 9 months of intervention. The pattern of fatty acids in serum VLDL-TGs was determined by ultracentrifugation followed by thin layer and gas chromatography, with the 18:1 n-9: 18:0 ratio providing an index of hepatic SCD1 activity.

Results

The hepatic SCD1 activity index correlated negatively with liver fat (r = −0.29, p = 0.04) and positively with insulin sensitivity, both OGTT-derived (r = 0.42, p = 0.003) and clamp-derived (r = 0.27, p = 0.07). These correlations depended on overall adiposity. They were absent in leaner participants (n = 27, liver fat: p = 0.34, insulin sensitivity [OGTT]: p = 0.75, insulin sensitivity [clamp]: p = 0.24), but were strong in obese individuals (n = 27, p = 0.004, p = 0.0002 and p = 0.006, respectively). Furthermore, during intervention a high SCD1 activity index at baseline predicted a decrease in liver fat only in obese participants (r = −0.46, p = 0.02).

Conclusions/interpretation

Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity.
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Metadata
Title
Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans
Authors
N. Stefan
A. Peter
A. Cegan
H. Staiger
J. Machann
F. Schick
C. D. Claussen
A. Fritsche
H.-U. Häring
E. Schleicher
Publication date
01-04-2008
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-0938-7

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