Medical Why does Von Gierke's disease give hypertriglyceridemia?

[sameeralord]

Hello guys,

This is what wiki says,

Hypertriglyceridemia resulting from amplified triglyceride production is another indirect effect of impaired gluconeogenesis, amplified by chronically low insulin levels. During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately glucose is impaired. Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of "metabolic control".

Now why do they say it is amplified by chronically low insulin levels. Hormone sensitive lipase which breaks down Triglycerides is inhibited by insulin. Lipoprotein lipase which breaks down Triglycerides is activated by insulin. Since insulin level is low in this case, how does low insulin levels increase TG level, it should decrease it right.

The only way I could see TG increasing is excess Acetyl CoA turned TG. Your help would be much appreciated. Thanks

 

[Monique]

Why are you using wikipedia?? The quote says

During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately glucose is impaired.

What? This is not correct in two ways: 1) during fasting you get an increased conversion of fatty acides into ketones, 2) ketones are not converted into glucose.

To answer your question, insulin inhibits the lipase that hydrolyzes triglycerides and thus inhibits release of fatty acids. In low insulin conditions you would have increased breakdown of fat and thus more free fatty acids.

 

[sameeralord]

Why are you using wikipedia?? The quote says What? This is not correct in two ways: 1) during fasting you get an increased conversion of fatty acides into ketones, 2) ketones are not converted into glucose.

To answer your question, insulin inhibits the lipase that hydrolyzes triglycerides and thus inhibits release of fatty acids. In low insulin conditions you would have increased breakdown of fat and thus more free fatty acids.

Hey thanks a lot for the help Monique Yes you are correct, however I'm still little bit confused with your last point. If there are more free fatty acid why do the call it hypertriglyceridemia, I mean if there is increased fat breakdown TG concentration must go down.

 

[Monique]

You are right, this is what's found on PubMed:

Hypoketotic hypoglycaemia and hypertriglyceridaemia are biochemical hallmarks of glycogen storage disease (GSD) 1. Increased malonyl coenzyme A production which compromises oxidation of long-chain fatty acids via carnitine palmitoyltransferase (CPT) 1 inhibition plays a crucial role in the pathogenesis of these complications.

There may be other reasons why there are increased levels of triglycerides, I'm sure there is a review paper on PubMed that will give an exact explanation

 

[Wallabie]

I think what was being implied by hypoinsulinemia causing the hypertriglyceridemia was, as originally suggested, insulin's effect on lipoprotein lipase. Lipoprotein lipase is required for the breakdown of triglycerides from VLDL in order to remove those triglycerides from the blood into the adipose tissue. Lipoprotein lipase is stimulated by insulin, so therefore in low insulin states triglycerides are not being cleared from the blood resulting in hypertriglyceridemia. This at least makes sense to me - I'm happy to be corrected though.

Also there is an element of glucose production from triglyceride breakdown and this achieved by converting the freed glycerol into DHAP and from there into glucose. Apparently it is quite a significant portion of the glucose production in a fasting state. I think the wikipedia quote was poorly worded.