Leucine supplementation has been studied as a possible therapeutic intervention for obesity and obesity-induced metabolic dysfunctions, and the researchers sought to assess its impact on obese, diabetic male mice.
The treatment mice were given leucine daily in drinking water for 12 weeks, while the controls were not given leucine.
Multiple benefits?
Subsequently, the researchers noted that daily leucine supplementation had reduced insulin resistance and impeded the progression of fatty liver in the treatment mice.
The latter result was further shown to be linked to reduced triglyceride synthesis in the liver, and leucine supplementation was also found to have ameliorated diabetic nephropathy in the mice.
In addition, leucine supplementation was reportedly responsible for reversing the disturbance to the mice's tricarboxylic acid cycle (a series of chemical reactions meant to release stored energy through the oxidation of an enzyme derived from fats, carbohydrates, carbon dioxide, protein and chemical energy).
This disturbance was indicated by progressively lower levels of citrate and succinate in the mice’s urine, something that was "significantly reversed" by dietary leucine supplementation.
Furthermore, an increased level of the metabolite indoxyl sulfate — associated with deteriorated kidney function — seen in the mice was ultimately reduced by leucine supplementation.
On the other hand, the mice's lowered carnitine levels (linked to the development of diabetes) were eventually increased by leucine supplementation.
The researchers hypothesised that these beneficial effects of AMPK (AMP-activated protein kinase), an enzyme instrumental in stabilising cellular energy.
These results are consistent with previous studies, wherein leucine supplementation was found to have anti-obesity, anti-diabetes and hepatoprotective effects (among others), either alone or in combination with other amino acids.
Amino acid factors
The researchers wrote that although branch-chain amino acids (BCAAs) linked to the activation of mTORC1 (a protein complex that controls protein synthesis and serves as a nutrient and energy sensor) could have a negative metabolic impact on obese mice, "many studies also showed that single leucine supplementation has potential metabolic benefits".
They concluded: "Dietary leucine exhibits metabolic benefits in obese, diabetic mice, including the attenuation of insulin resistance, hypertriglyceridemia, hepatic lipid accumulation, disturbance of the TCA cycle metabolism, and urinary carnitine levels.
"From current evidence, AMPK activation may be an important key issue. To clarify the contrary, further study to investigate the effects of BCAA mixture and isolated leucine on mTORC1 interaction in vivo and in vitro is needed."
Source: International Journal of Molecular Sciences
https://doi.org/10.3390/ijms19071921
"Dietary Leucine Supplement Ameliorates Hepatic Steatosis and Diabetic Nephropathy in db/db Mice"
Authors: Kuan-Hsing Chen, et al.