Stearoyl-CoA desaturase 1: Transcriptional regulation liver X receptor and its role in very low-density lipoprotein metabolism. by Kiki Chu

ISBN: 9781109048100

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NOOKstudy eTextbook

150 pages


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Stearoyl-CoA desaturase 1: Transcriptional regulation  by  liver X receptor and its role in very low-density lipoprotein metabolism. by Kiki Chu

Stearoyl-CoA desaturase 1: Transcriptional regulation by liver X receptor and its role in very low-density lipoprotein metabolism. by Kiki Chu
| NOOKstudy eTextbook | PDF, EPUB, FB2, DjVu, AUDIO, mp3, RTF | 150 pages | ISBN: 9781109048100 | 4.32 Mb

Stearoyl-CoA desaturase (SCD) is the rate-limiting enzyme responsible for the biosynthesis of monounsaturated fatty acids (MUFAs). MUFAs are important substrates for the synthesis of various kinds of lipids that are essential to many key biologicalMoreStearoyl-CoA desaturase (SCD) is the rate-limiting enzyme responsible for the biosynthesis of monounsaturated fatty acids (MUFAs). MUFAs are important substrates for the synthesis of various kinds of lipids that are essential to many key biological functions.

Therefore, determining the regulation of SCD is critical to the understanding of its role in different biological pathways. SCD1 isoform is primarily regulated at the level of gene transcription by many transcription factors, and identification of certain transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), has implicated a role of SCD1 in lipid metabolism. Subsequent studies with SCD1 deficient (SCD1-/-) mice further demonstrated an important role for SCD1 in lipid metabolism.

To further explore the role of SCD1 in lipid metabolism, transcriptional regulation of SCD1 gene by the nuclear receptor liver X receptor (LXR) was investigated. LXRs are important regulators of cholesterol and lipid homeostasis. Regulation of SCD1 gene by LXR was presumed to be primarily mediated by the master regulator of fatty acid synthesis SREBP-1c. However, here we demonstrated that SCD1 gene is also regulated by direct transcriptional activation by LXR through an LXR response element identified in the 5 promoter region of SCD1 gene. SCD1-/- mice were then employed to study the effect of SCD1 deficiency on LXR agonist T0901317-induced accumulation of hepatic and plasma triglyceride.

Upon T0901317-mediated LXR activation, SCD1-/- mice had reduced hepatic triglyceride accumulation and were markedly protected against plasma accumulation of triglyceride-rich very-low density lipoproteins (VLDLs). Further studies demonstrated that SCD1 deficiency did not reduce T0901317-induced secretion of large, triglyceride-rich VLDLs.

However, SCD1 deficiency did modulate the MUFA and saturated fatty acid (SFA) content of the triglycerides packaged onto the VLDLs, resulting in the attenuation of the T0901317-induced increase of MUFA to SFA ratio. This suggests that under T0901317-mediated LXR activation, SCD1-/- mice produce triglyceride-rich VLDL particles that are MUFA-poor or SFA-rich and may then protect against plasma triglyceride-rich VLDL accumulation by possibly increasing VLDL catabolism.

Together, these studies contribute to the understanding of the role of SCD1 in lipid metabolism and, more importantly, begin to shed light on its role in VLDL metabolism.



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