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

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 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 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.

Stearoyl-CoA Desaturase-1 Is Associated with Insulin Resistance in Morbidly Obese Subjects

“…These studies show discordant results concerning their relation with body mass index (BMI) and insulin resistance. A recent study showed that a high hepatic SCD1 activity index is associated with low liver fat content and high insulin sensitivity in obese participants (21). These data, together with those from previous animal studies (2,7,8,9,11,12), suggest that SCD1 may be involved in the regulation of insulin resistance in obesity.…”

Altered Fatty Acid Profile in the Liver and Serum of Stroke-Prone Spontaneously Hypertensive Rats: Reduced Proportion of cis-Vaccenic Acid

“…These findings emphasize the importance of understanding the mechanism regulating the production of fatty acid species. Moreover, the liver plays a key role in whole-body fatty acid metabolism, and fatty acid species that exist in the liver are considered to be pathophysiologically critical 23,26,27 . With regard to SHRSP, the lipid profile and fatty acid profile in renal membrane have been studied in relation to hypertension 28 .…”

Hepatic Lipid Composition and Stearoyl-Coenzyme A Desaturase 1 mRNA Expression Can Be Estimated from Plasma VLDL Fatty Acid Ratios

“…SCD1 mRNA expression is influenced by hormonal (1 ), nutritional (2 ), environmental, and genetic factors (3,4 ) and rapidly adjusts enzyme levels to the demands of the organism. Rodent and cell culture studies have suggested an important role of SCD1 in the pathogenesis of obesity (1,5 ), insulin resistance (1,5,6 ), diabetes mellitus (7 ), and atherosclerosis (8 -11 ) as well as inflammatory diseases (3,(12)(13)(14)(15)(16). Therefore, there has recently been considerable interest in the determination of SCD1 activity in human samples to elucidate the role of SCD1 for health and disease in clinical studies and interventions (3,4,(13)(14)(15)(16).…”

“…Rodent and cell culture studies have suggested an important role of SCD1 in the pathogenesis of obesity (1,5 ), insulin resistance (1,5,6 ), diabetes mellitus (7 ), and atherosclerosis (8 -11 ) as well as inflammatory diseases (3,(12)(13)(14)(15)(16). Therefore, there has recently been considerable interest in the determination of SCD1 activity in human samples to elucidate the role of SCD1 for health and disease in clinical studies and interventions (3,4,(13)(14)(15)(16). Apart from elegant stable isotope techniques to directly determine SCD1 desaturation activity in vivo (13 ), the ratios of SCD1 product and precursor fatty acids (18:1n9/18:0 and 16:1n7/16:0) in various accessible tissues (adipose tissue, skeletal muscle) have been used as a surrogate of enzyme activity in studies of small human cohorts (3,14,17 ).…”

“…For ethical reasons liver tissue samples available for clinical studies are scarce; thus we aimed to establish a blood marker representing hepatic SCD1 expression and activity. Because VLDL are assembled in the liver and secreted into the circulation (3,16,18 ) we hypothesized that VLDL-TG may reflect hepatic fatty acid composition and SCD1 expression.…”