Dietary nutrients are key to influencing metabolic health. Some recent studies have shown that a diet with reduced protein could influence longevity/metabolic health. One approach is dietary protein dilution (DPD), where protein is reduced and replaced by other nutrient sources. DPD has been suggested to promote metabolic remodeling and health but the precise nutritional components driving this response remain elusive. Moderate DPD has been shown to promote longevity in multiple species including flies, rodents, and perhaps humans.

Recent studies done at the Monash Biomedicine Discovery Institute (BDI) in Australia have provided a new understanding of the roles two essential amino acids (EAA) play in metabolic health, which may help in the fight against obesity.

The work can be found published in Nature Communications in a paper titled, “Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.”

The mouse studies show that restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD. More specifically, the group found that by reducing the amount of the two amino acids threonine and tryptophan, in young healthy mice, they were able to burn more calories than they consumed. Without calorie reduction they were kept lean and healthy, without the side-effect of lower muscle mass. A low-threonine diet even protected mice that were morbidly obese and prone to developing type 2 diabetes.

While a moderate reduction in dietary protein and therefore essential amino acids can enhance vitality, diets devoid of this component can make people sick very quickly and are not recommended. However, this study has shown that a reconsideration of the functions of these two amino acids in nutrition warrants further exploration.

By mimicking an amino acid supply from a casein-based diet, the team reported that they “demonstrated that restriction of dietary EAA, but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply.”

In addition, their findings showed that systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction.

“Once we understand which particular dietary components are needed for the health-promoting effects of these diets we can design strategies to mimic them, simulating the effects without having the negative side effects,” said Adam Rose, PhD, senior research fellow in biochemistry & molecular biology and senior author on the study.

Rose and his team genetically manipulated the mice to be able to synthesize the essential amino acid threonine, which blocked the health promoting effects of the low threonine diet and saw the mice gain weight, proving that these two amino acids can hold the key to a new diet approach.

The authors wrote that dietary threonine restriction (DTR) “retards the development of obesity-associated metabolic dysfunction” and that “liver-derived fibroblast growth factor 21 is required for the metabolic remodeling with DTR.”

Matthew Piper, PhD, senior lecturer at the School of Biological Sciences at Monash, and a co-author on the paper, added, “We are finding an increasing number of situations in which essential amino acids are powerful modulators of lifelong health and lifespan. Our findings on their specific effects gives us exciting insights into how we might harness their benefits to drive better health.”

“We are beginning to understand how critical the balance of dietary amino acids is to the control of appetite, health, and aging,” noted Stephen Simpson, PhD, academic director and professor, School of Life and Environmental Sciences of the University of Sydney’s Charles Perkins Centre.

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