Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation
| Autor: | James M. Ntambi, Makoto Miyazaki, Weng Chi Man, Kiki Chu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Receptors Steroid Hydrocarbons Fluorinated Receptors Retinoic Acid Coenzyme A Molecular Sequence Data Receptors Cytoplasmic and Nuclear Plasma protein binding Biology Response Elements digestive system chemistry.chemical_compound Mice High-density lipoprotein Internal medicine medicine polycyclic compounds Animals Humans Liver X receptor Molecular Biology Liver X Receptors Sequence Deletion Hypertriglyceridemia Pregnane X receptor Sulfonamides Triglyceride Base Sequence Cholesterol Cholesterol HDL Pregnane X Receptor food and beverages Cell Biology Articles Lipid Metabolism Orphan Nuclear Receptors Lipids DNA-Binding Proteins Endocrinology chemistry Saturated fatty acid lipids (amino acids peptides and proteins) Sterol Regulatory Element Binding Protein 1 Stearoyl-CoA Desaturase Protein Binding |
| Zdroj: | Molecular and cellular biology. 26(18) |
| ISSN: | 0270-7306 |
| Popis: | Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X receptor (LXR) and its role in plasma lipoprotein metabolism upon LXR activation. In vivo, the SCD1 gene remained induced upon LXR activation in the absence of sterol regulatory element-binding protein 1c (SREBP-1c), a known transcriptional regulator of SCD1. Serial deletion and point mutation analyses in reporter gene assays, as well as a gel mobility shift assay, identified an LXR response element in the mouse SCD1 promoter. In addition, SCD1 deficiency prevented the hypertriglyceridemic effect and reduced hepatic triglyceride accumulation associated with LXR activation despite induced hepatic expression of SREBP-1c protein and several SREBP1c and LXR target genes involved in lipoprotein metabolism. Unlike wild-type mice, SCD1-deficient mice failed to elevate the hepatic triglyceride monounsaturated acid (MUFA)/saturated fatty acid (SFA) ratio despite induction of the SCD2 gene. Together, these findings suggest that SCD1 plays a pivotal role in the regulation of hepatic and plasma triglyceride accumulation, possibly by modulating the MUFA-to-SFA ratio. In addition, SCD1 deficiency also increased plasma high-density lipoprotein cholesterol levels induced by LXR activation. |
| Databáze: | OpenAIRE |
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