Polymorphisms in the SCD1 Gene: Associations With Body Fat Distribution and Insulin Sensitivity

Abstract

Objective: Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme Adesaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans. Research Methods and Procedures:The study population was 1143 elderly Swedish men taking part of a populationbased cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis. Results: Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (␤) ϭ 1.19, p ϭ 0.007] and waist circumference (␤ ϭ Ϫ4.4, p ϭ 0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference. Conclusion:This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

“…For example, APOLD1 (apolipoprotein L domain containing 1), identified in HUVECs and EDG1 (sphingosine-1-phosphate receptor 1), identified in CBMCs, both regulate vascular function in mice and humans (Liu et al 2000;Regard et al 2004;Simonsen et al 2010;Gordon et al 2011). Even though no genes in placenta reached significance after multiple testing, polymorphisms in the genes ranked 1 and 2, HLA-B (major histocompatibility complex class 1B) and SCD (stearoyl-CoA desaturase), have been associated with low birth weight and metabolic disease, respectively, in humans (Warensjo et al 2007;Sampath and Ntambi 2008;Capittini et al 2009;Shin et al 2010). …”

Role of stearoyl-CoA desaturases in obesity and the metabolic syndrome

“…83 However, recently eight single nucleotide polymorphisms of the human SCD1 gene were reported to be associated with obesity and obesity-related insulin resistance. 84 Other contradictory evidence emerged from a study with obese diabetic patients treated with rosiglitazone to counter their insulin resistance. In these patients, SCD1 mRNA levels were elevated instead of downregulated.…”

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

“…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 ).…”

“…Stearoyl-coenzyme A desaturase 1 (SCD1) 4 is a microsomal enzyme that catalyzes ⌬9 desaturation as the limiting step of monounsaturated fatty acid synthesis (1 ). The cellular activity of the short-lived enzyme SCD1 is highly regulated and determined by the amount of enzyme present in the cell.…”

“…The cellular activity of the short-lived enzyme SCD1 is highly regulated and determined by the amount of enzyme present in the cell. 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).…”