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Are branched-chain amino acids the main culprit of dietary protein damaging metabolic health?

Jun 13, 2021

On April 22, 2021, Cell Metabolism published an online paper titled The adverse metabolic effects of branched-chain amino, with Dr. Yu Deyang from the University of Wisconsin as the first author and his supervisor Dudley W. Lamming as the corresponding author. acids are mediated by isoleucine and valine. The study found that isoleucine and valine in branched chain amino acids may be able to harm human health by affecting metabolism.

They found that among the three branched-chain amino acids, restricting the intake of isoleucine can almost completely produce the same metabolic effect as restricting the intake of all branched-chain amino acids. Limiting the intake of valine also produces a certain positive metabolic effect. Decreasing leucine is no different from the control group, which shows that isoleucine and valine, but not leucine, mainly mediate the adverse metabolic effects of branched chain amino acids. When a single branched-chain amino acid was added to the protein intake restricted diet group, the glucose tolerance and insulin sensitivity of the mice in the protein restricted diet supplemented with isoleucine were lower than those in the pure protein restricted diet group. Therefore, it is suggested that the positive metabolic effects of limiting protein intake need to be limited to isoleucine. Mice with limited intake of isoleucine rapidly reduced body fat component limitations, improved glucose tolerance and liver sensitivity to insulin.

In order to clarify the mechanism of the metabolic effect of limiting the intake of isoleucine, the researchers conducted liver metabolomics studies and analysis of serum metabolomics, and found that the ketone regeneration in the liver of mice that restricted the intake of isoleucine The pathway is significantly increased. The metabolic hormone FGF21 is expressed in multiple organs. UCP1-mediated subcutaneous fat fever (Thermogenesis), lipid regeneration (Lipogenesis), lipolysis (Lipolysis) and other key metabolic genes are also expressed. Increased, suggesting that the activation of these pathways mediates the lipid-lowering effect of isoleucine intake restriction. What's strange is that in FGF21 knockout mice, although the diet with restricted isoleucine intake can no longer significantly increase energy utilization (Energy Expenditure), it can still reduce body fat components and improve glucose tolerance. The mechanism of the metabolic effect of amino acid intake restriction is not completely mediated by FGF21.

Using the Western Diet-induced Obesity model of high-fat and high-sucrose-induced obesity to test the metabolic effects of single branched-chain amino acid restriction/addition, the researchers further proved that the intake of isoleucine and valine restriction can reduce fat and reduce fat. Re-enhance the effectiveness of metabolic health.

Finally, through the dietary survey and analysis of the local population in Wisconsin, the researchers found that the level of isoleucine in dietary protein was positively correlated with body mass index (BMI), and those with higher intake of isoleucine in dietary protein were more likely Have a higher body mass index. These findings clearly confirm that isoleucine and valine have adverse metabolic effects, and suggest that restricting the intake of isoleucine and valine through dietary pathways may become a feasible diet therapy for weight loss and lipid reduction to promote metabolic health.