Atkins diet and its consequence on cholesterol metabolism?

[MudPhud20XX]

So one of the Kaplan questions says:

A person goes on the Atkins diet of high fat, high protein, and no carbohydrate. Which statement best describes the effect of the diet on this person?

The answer is "The person would be unable to synthesize cholesterol because glucagon inhibits cholesterol synthesis."

So I get that with no-carb diet, there will be no insulin and elevated glucagon, which inhibits HMG CoA, but in reality, this person can still make cholesterol via gluconeogenesis, right? Gluconeogenesis will make acetyl-CoA, which will enter into the cholesterol metabolism, correct?

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[Myxedema]

Is this a question from their Qbank? I don't recall this one from Qbook. Anyway, like you've said, the key issue with this question is about the regulation of HMG-CoA reductase, which is stimulated by insulin & inhibited by glucagon. Since carbohydrates are the main trigger from insulin release, a person with a low carbohydrate diet would be as if it is in fasting state (low insulin, high glucagon). Besides that, I'm quite sure the actual metabolic event is regulated in a much more complex manner. Just know what regulates HMG-CoA reductase and it should be enough.

 

[MudPhud20XX]

No, the question was from online quizzes you get after the online lectures. Thanks for the explanation!

 

[notbobtrustme]

that's poor wording. The liver would still synthesize cholesterol since it's a necessary part of cellular membranes. However, the overall level would decrease because serum lipoproteins would be decreased in response to less insulin.

 

[ulikedaggers]

So one of the Kaplan questions says:

A person goes on the Atkins diet of high fat, high protein, and no carbohydrate. Which statement best describes the effect of the diet on this person?

The answer is "The person would be unable to synthesize cholesterol because glucagon inhibits cholesterol synthesis."

So I get that with no-carb diet, there will be no insulin and elevated glucagon, which inhibits HMG CoA, but in reality, this person can still make cholesterol via gluconeogenesis, right? Gluconeogenesis will make acetyl-CoA, which will enter into the cholesterol metabolism, correct?

Atkins diet = lots of dietary cholesterol = decreased transcription of HMG CoA Reductase and proteolysis of existing HMG Coa Reductase = no endogenous cholesterol formation.

 

[Phloston]

This is why I hate Kaplan. They just confuse students and, not to mention, discuss things in a way never known to be tested on Step1.

I'd say the Atkin's diet decreases cholesterol synthesis mainly because endogenous cholesterol synthesis is predominantly carbohydrate-, not lipid-, dependent. It's all about the net amount of glycolytic intermediates (and therefore acetyl-CoA) yielded from food consumed. That's why diets high in fructose increase cholesterol. It's also why many patients who find out they have high LDL actually experience exacerbated cholesterol levels after trying a month of "improved diet" before starting statins, because they cut out all of their fats and instead consume more carbs. If you've ever heard stories of people with high cholesterol who have had their levels skyrocket after first trying to modify their diet, that's why. I would recommend any patient with high LDL try the Atkin's diet for a month before coming back for follow-up.

Apart from that, even the Atkin's diet would cause secretion of insulin. What about glucose-dependent insulinotropic peptide? It's right in FA in the GI chapter, and it's tested in QBanks as the only GI hormone stimulated in response to carbs, fat AND protein. Cutting out sugar would still increase GDIP, and GDIP secretion causes insulin to go up.

I'd say Kaplan's explanation is the definition of a pigeonhole.

 

[BurberryDoc]

So one of the Kaplan questions says:

A person goes on the Atkins diet of high fat, high protein, and no carbohydrate. Which statement best describes the effect of the diet on this person?

The answer is "The person would be unable to synthesize cholesterol because glucagon inhibits cholesterol synthesis."

So I get that with no-carb diet, there will be no insulin and elevated glucagon, which inhibits HMG CoA, but in reality, this person can still make cholesterol via gluconeogenesis, right? Gluconeogenesis will make acetyl-CoA, which will enter into the cholesterol metabolism, correct?

HMG-CoA Reductase is regulated at 4 levels - one of these levels is the release of a bHLH Tx factor under the control of local cholesterol concentration. If cholesterol is high, the bHLH will be retained in the membrane (the specific mechanism by which escaped me at the moment, but basically some membrane protein cleavage must occur for the bHLH to be released, but in the presense of cholesterol this is inhibited) and so (a) you have decreased synthesis of HMG-CoA Reductase, but also (b) just because you have synthesis of Acetyl-Coa as an eventual result of metabolism of glucose derived from gluconeogenesis, you cannot proceed further in the cholesterol biosynthetic pathway past HMG-CoA Reductase if the HMG-CoA reductase levels are inappreciably low!

Also, as I understand it, the diabetic dyslipidemia observed in DM-2 is a result of the loss of (+) effect of insulin on HMG-CoA reductase. I cannot recall if Glucagon is a direct (-) effector of HMG-CoA Reductase or not, but I imagine that it could either be due to an increase in glucagon (due to the typically low blood glucose observed in a carb-restricted diet) or just a "dis-activation" of HMG-CoA reductase given the reciprocal fall in insulin.


Source: I am a 2nd year biochemistry graduate student

 

[sanj238]

This is why I hate Kaplan. They just confuse students and, not to mention, discuss things in a way never known to be tested on Step1.

I'd say the Atkin's diet decreases cholesterol synthesis mainly because endogenous cholesterol synthesis is predominantly carbohydrate-, not lipid-, dependent. It's all about the net amount of glycolytic intermediates (and therefore acetyl-CoA) yielded from food consumed. That's why diets high in fructose increase cholesterol. It's also why many patients who find out they have high LDL actually experience exacerbated cholesterol levels after trying a month of "improved diet" before starting statins, because they cut out all of their fats and instead consume more carbs. If you've ever heard stories of people with high cholesterol who have had their levels skyrocket after first trying to modify their diet, that's why. I would recommend any patient with high LDL try the Atkin's diet for a month before coming back for follow-up.

Apart from that, even the Atkin's diet would cause secretion of insulin. What about glucose-dependent insulinotropic peptide? It's right in FA in the GI chapter, and it's tested in QBanks as the only GI hormone stimulated in response to carbs, fat AND protein. Cutting out sugar would still increase GDIP, and GDIP secretion causes insulin to go up.

I'd say Kaplan's explanation is the definition of a pigeonhole.

Not sure about all the hate for Kaplan. I actually had a question like this on USMLERX but differently. They asked what happens to an obese person who goes on a diet (basically forced starvation) and had similar choices.

Its a relevant question as it asks you to understand the concept behind what is involved in cholesterol and fat use/formation. Obviously you understand the concepts well 🙂