Pathoma - clofibrate and cholesterol stones?

[DrJonesss]

So in Chapter 11, Dr. Sattar states that clofibrate increases the risk for cholesterol stones because it upregulates HMG CoA reductase. Uh...wat.

This wasn't addressed in the errata, and I can't really find a concise explanation anywhere, can anyone explain why clofibrate increases the risk of forming cholesterol stones? Thanks!

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[CassieBagley]

Clofibrate activates LPL, which stimulates conversion of VLDL to LDL and LDL to IDL. C-II activates LPL and I think it's only on VLDL and LDL, so most of those 2 guys get shunted to IDL while their released TGs & cholesterol get taken up into adipose and skeletal muscle. However, so much LPL activity is activated by clofibrate that some of the TGs and cholesterol remain in the blood and get transported to liver. The liver will re-package these into VLDL again, but still some cholesterol/TG is left over, so they get shunted to bile acid pathway. Saturation of bile acids with cholesterol facilitate GS formation. Think of someone losing a lot of weight: LPL will be activated because the body wants all that fat from the newly made VLDLs from the diet....explaining why sudden weight loss is also a risk factor for GS.

 

[fleshwound]

Clofibrate activates LPL, which stimulates conversion of VLDL to LDL and LDL to IDL. C-II activates LPL and I think it's only on VLDL and LDL, so most of those 2 guys get shunted to IDL while their released TGs & cholesterol get taken up into adipose and skeletal muscle. However, so much LPL activity is activated by clofibrate that some of the TGs and cholesterol remain in the blood and get transported to liver. The liver will re-package these into VLDL again, but still some cholesterol/TG is left over, so they get shunted to bile acid pathway. Saturation of bile acids with cholesterol facilitate GS formation. Think of someone losing a lot of weight: LPL will be activated because the body wants all that fat from the newly made VLDLs from the diet....explaining why sudden weight loss is also a risk factor for GS.

I've heard of that, as well as another mechanism by which clofibrate blocks 7alpha-hydroxylase (converts cholesterol to bile acid) so it decreases bile acids causing cholesterol to precipitate out.

 

[Phloston]

I've heard of that, as well as another mechanism by which clofibrate blocks 7alpha-hydroxylase (converts cholesterol to bile acid) so it decreases bile acids causing cholesterol to precipitate out.

Yeah, this is right.