Since LXRs were discovered, there has been considerable interest in developing p
ID: 61601 • Letter: S
Question
Since LXRs were discovered, there has been considerable interest in developing pharmacologic therapeutics that would act as LXR agonists to promote reverse-cholesterol transport. As investigators studied these agonists, they found that SREBP1c is also a target of LXR (especially in the liver). Although transient, treatment of animals with LXR agonists led to a significant elevation in plasma triacylglycerol concentration. Discuss and explain the molecular mechanism(s) that contribute to this potentially adverse side effect.Explanation / Answer
LXR (liver X receptor) are nuclear receptor family transcription factors, agonists are the activators of LXR.
As I know that, the LXR typically involve in the cholesterol transport and efflux. It regulates the fatty acid synthesis and lipid homeostasis. It's agonists suppresses the expression apolipoprotein A5 (APOA5) and induces the VLDL-triglyceride hydrolysis which resulting from increased expression of hepatic LPL mRNA that enhances the hydrolysis of triglycerides rich lipids, eventually leads to increased plasma triglyceride levels. In addition, it activates the SREBP-1c, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD) that are helpful in the lipogenesis and upregulation of hepatic and plasma triglycerides.