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.
Specifically, the amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in monocytes and macrophages was identified as the primary mechanism responsible, rather than the elevated levels of cholesterol and saturated associated with the consumption of animal protein – meat.
Leucine is a branched-chain amino acid, is essential in regulating animal growth and development, with an underlying anabolic effect on muscle and other tissues, including the ability to stimulate protein synthesis by activating the mTORC1 signalling pathway – a process enhanced by consuming carbohydrates and essential amino acids.
And importantly, consuming more than ∼25 g of protein per meal was found to be the threshold where the volume of leucine required significantly increased mTOR activation.
Lead authors, Dr Bettina Mittendorfer from the Washington University School of Medicine, and Dr Babak Razani from the University of Pittsburgh School of Medicine pointed out that the relationship between leucine and mTORC was described more than a decade ago and had already been identified as a potential supplement for human health.
“The amino acid found to promote muscle growth and metabolic health in animals and humans, as well as benefit lipid metabolism and insulin sensitivity, making it a promising strategy for preventing and treating metabolic diseases, including type 2 diabetes and obesity,” they said.
“It aids in the upkeep of strong bones, controls blood sugar, and promotes a robust immune system. Inadequate leucine intake has been linked to various health issues that may reduce quality of life. To maintain a healthy and robust body, consuming enough leucine-rich meals or supplements is essential.”
These effects appear to be due to leucine’s ability to stimulate thermogenesis, increase fatty acid oxidation, and improve insulin signalling, which can promote healthy glucose metabolism and weight loss.
The possibility that leucine was one of the “active components” in high-protein diets has prompted interest in studying its potential medicinal uses, and in a series of clinical studies that involved graded amounts of protein ingestion together with detailed plasma amino acid analysis and human monocyte/macrophage experiments, the team discovered that leucine was the key activator of mTOR signalling in macrophages.
Leucine is found in meat, chicken, fish, eggs, and dairy products. For example, three ounces of chicken breast or beef have around 1.5 g of leucine, whereas a cup of milk or yoghurt contains about 0.7 g. Leucine is also found in beans, lentils, peas, soy products, and whole grains.
“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 more than ∼22% of dietary energy requirements drives atherosclerosis in male mice,” the authors said.
“The culmination of our work highlights a mechanism whereby dietary protein intake and specifically leucine intake, induces dose-dependent mTORC1-mediated inhibition of autophagy-lysosomal degradation in monocytes/macrophages to promote atherogenesis.
“This discovery provides a key mechanistic link between dietary protein and atherosclerotic cardiovascular disease risk that can help redefine dietary protein intake recommendations and can perhaps be leveraged as a therapeutic strategy.”
The findings have particular relevance for people working on their anaerobic strength in the gym, given the cultural obsession with protein shakes and nutritional supplements associated with the ‘fitness’ lifestyle.
According to the Journal of the International Society of Sports Nutrition, it has been proposed that muscle protein synthesis is maximized in young adults with an intake of ~ 20–25 g of a high-quality protein; anything above this amount is believed to be oxidized for energy or transaminated to form urea and other organic acids.
In a study often cited as support for the hypothesis that MPS is maximized at a protein dose of ~ 20–25 g, in 2013 Areta et al. provided different amounts of protein to resistance-trained participants over a 12-h recovery period following performance of a multi-set, moderate repetition leg-extension exercise.
“A total of 80 g of whey protein was ingested in one of the following three conditions: 8 servings of 10 g every 1.5 h; 4 servings of 20 g every 3 h; or 2 servings of 40 g every 6 h. Results showed that MPS was greatest in those who consumed 4 servings of 20 g of protein, suggesting no additional benefit, and actually a lower rise in MPS when consuming the higher dosage (40 g) under the conditions imposed in the study,” the authors said.
“However, these findings are specific to the provision of fast-digesting proteins without the addition of other macronutrients. Consumption of slower-acting protein sources, particularly when consumed in combination with other macronutrients, would delay absorption and thus conceivably enhance the utilization of the constituent amino acids.”