Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk

[Seagal]

Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk - Nature Metabolism

Zhang et al. use human studies and mechanistic work in mouse models to describe how leucine serves as the key amino acid derived from dietary protein to drive deleterious macrophage mTORC1 signalling and promote cardiovascular disease.

www.nature.com

High protein intake is common in western societies and is often promoted as part of a healthy lifestyle; however, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischaemic cardiovascular disease. In a series of clinical studies on male and female participants (NCT03946774 and NCT03994367) that involved graded amounts of protein ingestion together with detailed plasma amino acid analysis and human monocyte/macrophage experiments, we identify leucine as the key activator of mTOR signalling in macrophages. We describe a threshold effect of high protein intake and circulating leucine on monocytes/macrophages wherein only protein in excess of ∼25 g per meal induces mTOR activation and functional effects. By designing specific diets modified in protein and leucine content representative of the intake in the general population, we confirm this threshold effect in mouse models and find ingestion of protein in excess of ∼22% of dietary energy requirements drives atherosclerosis in male mice. These data demonstrate a mechanistic basis for the adverse impact of excessive dietary protein on cardiovascular risk.

 

[ajax31]

https://chrismasterjohnphd.substack.com/p/will-eating-protein-wreck-your-arteries?utm_source=post-email-title&publication_id=752142&post_id=141894759&utm_campaign=email-post-title&isFreemail=true&r=1d5vap&open=false&utm_medium=email

 

[sammmy]

Another "study". Basically they prove that feeding the immune system with a fast absorbing energy source (we already knew about sugar, now it is leucine from protein isolates): (1) activates mTOR, (2) leads to acceleration of atherosclerosis in rats genetically engineered to develop atherosclerosis.

They didn't use real food in the human studies which showed the mTOR activation - first it was some processed protein/carb shake, then it was blended carbs but with protein isolates, not real meat. How is that relevant to eating real food like meat?

Don't eat concentrated fast sugar, don't eat concentrated fast protein (it's NOT natural) and you won't have any of that problem, considering that you are not genetically engineered mouse.

Eskimos ate only meat and didn't have any cardiovascular diseases. End of story!

 

[Fernando Almaguer]

Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk - Nature Metabolism

Zhang et al. use human studies and mechanistic work in mouse models to describe how leucine serves as the key amino acid derived from dietary protein to drive deleterious macrophage mTORC1 signalling and promote cardiovascular disease.

www.nature.com

High protein intake is common in western societies and is often promoted as part of a healthy lifestyle; however, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischaemic cardiovascular disease. In a series of clinical studies on male and female participants (NCT03946774 and NCT03994367) that involved graded amounts of protein ingestion together with detailed plasma amino acid analysis and human monocyte/macrophage experiments, we identify leucine as the key activator of mTOR signalling in macrophages. We describe a threshold effect of high protein intake and circulating leucine on monocytes/macrophages wherein only protein in excess of ∼25 g per meal induces mTOR activation and functional effects. By designing specific diets modified in protein and leucine content representative of the intake in the general population, we confirm this threshold effect in mouse models and find ingestion of protein in excess of ∼22% of dietary energy requirements drives atherosclerosis in male mice. These data demonstrate a mechanistic basis for the adverse impact of excessive dietary protein on cardiovascular risk.

what do you have to say to the rebuttals of these gentlemen above sir?

 

[Seagal]

what do you have to say to the rebuttals of these gentlemen above sir?

I'm just sharing this abstract. I don't have access to the paper. I find the mechanistics part of that research interesting. However, I'm 'surprised' about how the authors jump to conclusions about nutrition recommendations. I have the impression that our research community is politicized. Plant protein contains less Leucin...
I think our metabolism runs through cycles of anabolism and catabolism. Catabolism in the sense of cleaning up, breaking down 'unwanted' stuff.
I think that pushing our bodies (by PEDs, nutrition, training) towards 24/7 max anabolism is deleterious to health in the long term.

 

[Fernando Almaguer]

I'm just sharing this abstract. I don't have access to the paper. I find the mechanistics part of that research interesting. However, I'm 'surprised' about how the authors jump to conclusions about nutrition recommendations. I have the impression that our research community is politicized. Plant protein contains less Leucin...
I think our metabolism runs through cycles of anabolism and catabolism. Catabolism in the sense of cleaning up, breaking down 'unwanted' stuff.
I think that pushing our bodies (by PEDs, nutrition, training) towards 24/7 max anabolism is deleterious to health in the long term.

Yeah I think balancing the catabolism with anabolism is key also.