Sterculic Oil, a natural inhibitor of SCD1, improves the metabolic state of obese OLETF rats

Abstract

Abnormal lipid metabolism and excess accumulation of lipid in non-adipose tissues are defining characteristics of obesity and its comorbidities. Expression and/or activity of stearoyl-CoA desaturase-1 (SCD1), a major regulator of lipid metabolism, is increased with obesity and the reduction/ablation of this enzyme is associated with an improved metabolic profile. Sterculic oil (SO), obtained from the seeds of the Sterculia feotida tree, contains a high concentration of cyclopropenoic fatty acids which are known inhibitors of SCD1. The purpose of this study was to determine the effects of SO supplementation on the development of obesity and insulin resistance in hyperphagic, obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats received either an AIN-93G diet (control) or an AIN-93G diet containing 0.5% SO for 10 weeks. SO did not alter body weight or body composition. Importantly, the desaturase indices, a proxy for the activity of SCD1, were reduced in the liver and adipose tissue of SO supplemented animals. This reduction in SCD1 activity was associated with a reduction in fasting blood glucose concentrations and improved glucose tolerance. In addition, SO reduced intra-abdominal fat mass and adipocyte size and resulted in a ∼3-fold increase in GLUT1 gene expression in intra-abdominal fat. Liver triglyceride content and lipogenic gene expression were reduced by SO. Consistent with an improved metabolic phenotype, SO also improved plasma cholesterol, LDL-cholesterol, and triglyceride concentrations. Overall, our data demonstrate an improved metabolic phenotype with SO supplementation and suggest further studies are required to better understand the therapeutic potential of SO.