Premium
Investigating the anti‐hypertriglyceridemic effect of Stearoyl‐CoA Desaturase 1 deficiency under liver X receptor activation
Author(s) -
Chu Kiki,
Ntambi James M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.807.14
Subject(s) - medicine , chemistry , endocrinology , very low density lipoprotein , liver x receptor , triglyceride , stearoyl coa desaturase , lipoprotein lipase , lipoprotein , enzyme , nuclear receptor , gene expression , biochemistry , cholesterol , biology , gene , transcription factor
Stearoyl‐CoA desaturase (SCD) is the rate‐limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. Previously, we showed that 129SvEv mice with targeted disruption of the SCD1 gene (SCD1−/−) exhibit reduced hepatic triglyceride (TG) synthesis and reduced levels of TGs in very low‐density lipoprotein (VLDL) fractions. Furthermore, in recent studies we showed that SCD1 deficiency prevented the hypertriglyceridemic effect and reduced hepatic TG accumulation upon liver X receptor (LXR) activation with a synthetic agonist T0901317. To investigate the anti‐hypertriglyceridemic effect of SCD1 deficiency under LXR activation, hepatic TG production rate was determined by measuring the appearance of plasma TG under conditions in which TG hydrolysis by lipoprotein lipase (LPL) is inhibited using Poloxamer 407. Both wild‐type and SCD1−/− mice showed the same level of increase in the rate of hepatic TG production under LXR activation, suggesting that the ability of SCD1−/− mice to secrete TG rich‐VLDL particles is not impaired. In addition, induction of hepatic LPL gene expression upon LXR activation was significantly higher in the SCD1−/− mice compared to wild‐type counterpart. These results suggest that the lack of increase in plasma TG upon LXR activation in SCD1−/− mice may be due to increase in the clearance of TG rich‐VLDL particles via an increase in the hydrolysis of VLDL‐TG by LPL.