Cholesterol metabolism and fat metabolism question Use the article provided belo

Question

Cholesterol metabolism and fat metabolism question

Use the article provided below as reference to answer the question

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(3 Points) 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 antagonists induce several genes that involve in the regulation of cholesterol homeostasis, lipogenesis and reverse cholesterol transport, apolipoprotein E (apoE), lipoprotein lipase, and sterol response element-binding protein 1-c (SREBP1-c). Agonists of LXRs increase the biosynthesis of fatty acid and secretion of very low-density lipoproteins (VLDL). This indicates transient increase in plasma triglycerides. This effect also might be due to the increased lipid uptake. Most importantly, LXR agonists significantly induce the LPL mRNA expression in the liver, which in turn leads to increased triglyceride-rich lipoprotein hydrolysis and liver fatty acid uptake that results in plasma hypertriglyceridemia.

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