Does l-leucine supplementation cause any effect on glucose homeostasis in rodent models of glucose intolerance? A systematic review
l-Leucine has been used to improve metabolic outcomes in glucose-intolerant rodent models. However, because studies have used different experimental models and conditions it is difficult to establish the best approach for new clinical trials evaluating the potential effects of l-leucine on glucose homeostasis. We performed a systematic review to report the effect of l-leucine supplementation on glucose homeostasis in rodents with glucose intolerance. The search engines MEDLINE and ScienceDirect were applied using MeSH terms. Thirty-four studies were included in this systematic review. Based on the current data, ingestion of 90–140 mg day−1 of isolated l-leucine in diet-induced obesity (DIO) models shows improvement in metabolic markers if offered during the development of the metabolic disorder in almost all the studies, but not after. Branched-chain amino acid supplementation was effective in streptozotocin-induced β-cells death but not in DIO models. l-Leucine supplementation seems to have an optimal dose and timing for supplementation to improve glucose homeostasis in DIO.
KeywordsLeucine Glucose homeostasis Insulin resistance Obesity Diabetes
This research did not receive any specific grant from funding agencies in public, commercial or not-for-profit sectors. The corresponding author is funded by the National Council for Scientific and Technological Development (CNPq) and is a CNPq Research Productivity Fellow. The first and the second authors received Ph.D. scholarships from the Coordination for the Improvement of Higher Education Personnel (CAPES).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any experimental procedure with human participants or animals performed by any of the authors.
- Chen C, Yu X, Shao S (2015) Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: a meta-analysis. PLoS One 10:1–14Google Scholar
- Etxeberriaa U, Garzaa AL, Martínez JL, Milagro FI (2015) Biocompounds attenuating the development of obesity and insulin resistance produced by a high-fat sucrose diet. Nat Prod Commun 10:1417–1420Google Scholar
- Fu L, Li F, Bruckbauer A, Cao Q, Cui X, Wu R, Shi H, Xue B, Zemel MB (2015) Interaction between leucine and phosphodiesterase 5 inhibition in modulating insulin sensitivity and lipid metabolism. Diabetes Metab Syndr Obes 6(8):227–239Google Scholar
- Li H et al (2016) Leucine supplementation increases SIRT1 expression and prevents mitochondrial dysfunction and metabolic disorders in high-fat diet-induced obese mice. Am J Physiol Endocrinol Metab 15(303):1234–1244Google Scholar
- Liu R, Li H, Fan W, Jin Q, Chao T, Wu Y, Huang J, Yang X (2017) Leucine supplementation differently modulates branched-chain amino acid catabolism, mitochondrial function and metabolic profiles at the different stage of insulin resistance in rats on high-fat diet. Nutrients 9:565–585CrossRefGoogle Scholar
- Tremblay F, Marette A (2001) Amino acids and insulin signaling via the mTOR/p70 S6 kinase pathway. J Biochem Chem 276(41):38052–38060Google Scholar
- Zhao X et al (2016) The relationship between branched-chain amino acid related metabolomic signature and insulin resistance: a systematic review. J Diabetes Res 1–12Google Scholar
- Zskudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50:536–546Google Scholar