Abstract
BackgroundLeucine deprivation modulates the dietary amino acid composition, reducing the fat content and improving the glucose tolerance, thus protecting the organism against obesity. However, a complete deprivation of leucine can lead to an extremely rapid fat loss in mice, accompanied by prolonged adverse effects such as weakness and mental fatigue. Therefore, in this study we aimed to seek the optimal concentration of dietary leucine that can reduce fat mass and improve the metabolism without the onset of severe effects.MethodsTo investigate whether there is a better concentration of diet leucine restriction (LR), based on the diet we conducted (A10021B), that can reduce fat mass and improve metabolism status without taking many negative effects, we fed 8 weeks old male C57Bl/6J mice with increasing degrees of leucine restriction diet 0% LR (control group), 25% LR, 50% LR, and 75% LR groups (4–6 mice each group). Fat mass and blood glucose levels were measured. The expression levels of genes involved in lipid metabolism in white adipose tissue (WAT) and liver, and proteins in insulin signaling were assessed in WAT, liver and muscle.ResultsWe found that the 50% LR group is the most proper group here at the lowest leucine effective concentration, which reduced fat mass (p < 0.05) and improved glucose regulation in mice over a 90 days feeding. Further studies revealed that lipid synthesis pathway (Fas, Scd1and Srebp1, p < 0.05) was downregulated and lipolysis (Atgl, p < 0.05) was upregulated in WAT in 50% LR group, compared to that in control group. Furthermore, glucose regulation (glucose tolerance test, p < 0.05) was also improved, and insulin signaling (p < 0.05) in the muscle was enhanced in 50% LR group while in WAT and liver were not changed.ConclusionsCollectively, a 50% LR in mice reduced fat mass and improved glucose regulation, which may function through modulating lipid synthesis and lipolysis pathway in adipose tissue as well as enhancing insulin signaling in muscle. So far, we provide a further consideration for carrying out the diet of leucine restriction to reduce fat and improve metabolism status before clinical study.
Highlights
Leucine deprivation modulates the dietary amino acid composition, reducing the fat content and improving the glucose tolerance, protecting the organism against obesity
We provide a further consideration for carrying out the diet of leucine restriction to reduce fat and improve metabolism status before clinical study
We found that 50% leucine restriction (LR) is the better concentration here based on our diet composition that can lead to fat loss by downregulating lipid synthesis and upregulating lipolysis in white adipose tissue (WAT), and glucose tolerance improvement by enhancing insulin signaling in muscle
Summary
Leucine deprivation modulates the dietary amino acid composition, reducing the fat content and improving the glucose tolerance, protecting the organism against obesity. Dietary restriction is a nutritional intervention with clear health benefits as it moderately reduces food intake, protects against multiple diseases, including obesity, cardiovascular disease, and diabetes, and extends life span in rodents [3]. Many of the effects of dietary restriction on longevity and health span in model organisms have been linked to reduced protein and amino acid (AA) intake and the stimulation of specific nutrient signaling pathways [5, 6]. Protein or essential amino acid (EAA) restriction extends both lifespan and healthspan in rodents and reduces diabetes, cancer, and overall mortality in humans [7,8,9]. Interventions aimed at lowering the intake of proteins or specific AAs can be beneficial and have the potential to be widely adopted and effective in preventing obesity and optimizing healthspan [9]
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