All About Lipogenesis

[yerrag]

In the article it's mentioned that substances that block excess lipolysis help reduce fat by reducing fat accumulation in the liver and rest of the body.

How does this work exactly? I would've thought that anything that increases lipolysis automatically reduces fat.

I wondered about that as well. You'd have to have fat to begin with in order to undergo lipolysis. It makes sense that preventing the breakdown of fat into fatty acids would keep fat from being formed, but it's kinda like saying that to keep fat from being made, you shouldn't be breaking down existing fat stores into fatty acids so that they won't be available to be made back into fats.

 

[yerrag]

I can’t understand how so many people still think that eating specific carbs is going to make a difference vs other “better” carbs.

The only things that matter are calories in+out and nutrient density.

A high fat diet combined with carbs is terrible in terms of palatability (terribly good = overeating) and that’s the issue at hand. Bread with cheese. Whole milk. Rice or pasta with a nice sauce. Full fat yogurt with manmade “improved” fruits.

Virtually every single third world country eats a diet loaded with carbs, and naturally low in fats. Get out of the Western degeneration and YouTube quackery

Welcome to the Ray Peat Forum!

 

[Hans]

I thought more about this, and I wonder if there's validity to the argument that you need to have a large amount of fructose intake for the liver to convert it to fat via de novo lipogenesis (DNL). This argument assumes pretty much that DNL in the liver is the significant, if not the only, way that DNL is accomplished. But my understanding is that during hyperglycemia, the body has a mechanism of converting glucose to fructose. I see this as an adaptive mechanism for the body to lower blood sugar, as fructose can be turned into lactate, as lactate can then be turned into fat, where in storage it does no harm. Because the body can turn fructose into lactate and into fat, it makes me question the argument that a large intake of fructose is needed for the liver to convert it to fat.

I'm assuming that lactate converting into fat does not require the liver to do anything though. @Hans do you know if the liver is needed for lactate to convert to fat?

DNL isn't really significant anywhere in the body and fructose doesn't have to be converted to lactate first. Keep in mind that citrate is one of the main precursors for DNL, but lactate can also contribute. During hyperglycemia, insulin will most likely also be high and then under such circumstances will DNL be upregulated, which converts glucose and fructose to fats. Lactate is not that much of a contributor. During exercise when lactate is created, it's transported to the liver where it's reconverted to glucose to be used as fuel again, but it's rather energy-intensive.

In the article it's mentioned that substances that block excess lipolysis help reduce fat by reducing fat accumulation in the liver and rest of the body.

How does this work exactly? I would've thought that anything that increases lipolysis automatically reduces fat.

Excess lipolysis floods the liver with fat and when the liver cannot export or oxidize it fast enough, it accumulates. So blocking lipolysis can help the liver recover. Plus, if you just upregulate lipolysis but nothing is happening with the fat, it just re-esterifies. It's a futile cycle.

 

[Peater Piper]

Hey all,

Just a while ago there was some talk about lipogenesis so I wrote an article on it to try help get rid of misconceptions on lipogenesis.

Hope you enjoy and let me know what you think.
The Ultimate Guide on Lipogenesis

Oops! That page can’t be found.​

Any chance this is uploaded elsewhere? I'm dealing with a tumor that is apparently the result of a lack of tumor suppressor Merlin. The result is uncontrolled lipogenesis which prevents apoptosis, so I'm looking for the best ways to limit lipogenesis.

An essential role for the tumor suppressor Merlin in regulating fatty acid synthesis

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of the NF2 gene encoding the protein ...

www.ncbi.nlm.nih.gov

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of the NF2 gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear. We report here that Nf2-deficient cells display elevated expression levels of key enzymes involved in lipogenesis and that this upregulation is caused by increased activity of Torc1. Inhibition or knockdown of fatty acid synthase (FASN), the enzyme that catalyzes the formation of palmitic acid from malonyl-CoA, drove NF2-deficient cells into apoptosis. Treatment of NF2-mutant cells with agents that inhibit the production of malonyl-CoA reduced their sensitivity to FASN inhibitors. Collectively, these results suggest that the altered lipid metabolism found in NF2-mutant cells renders them sensitive to elevated levels of malonyl-CoA, as occurs following blockade of fatty acid synthase, suggesting new targeted strategies in the treatment of NF2-deficient tumors.