Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans.
OBJECTIVE
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 (1)H-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
Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity.
Stefan
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Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de
Peter
A
A
Cegan
A
A
Staiger
H
H
Machann
J
J
Schick
F
F
Claussen
C D
CD
Fritsche
A
A
Häring
H-U
HU
Schleicher
E
E
D000328:Adult; D000368:Aged; D001823:Body Composition; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D005234:Fatty Liver / Q000201:enzymology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology*; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*; D015431:Weight Loss
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D013230:Stearoyl-CoA Desaturase