Leucine Supplementation Protects from Insulin Resistance by Regulating Adiposity Levels

Abstract

BackgroundLeucine supplementation might have therapeutic potential in preventing diet-induced obesity and improving insulin sensitivity. However, the underlying mechanisms are at present unclear. Additionally, it is unclear whether leucine supplementation might be equally efficacious once obesity has developed.Methodology/Principal FindingsMale C57BL/6J mice were fed chow or a high-fat diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD-fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity level comparable to that of HFD-Leu mice. Finally, a third group of mice was exposed to HFD for 12 weeks before being chronically supplemented with leucine. Leucine supplementation in HFD-fed mice decreased body weight and fat mass by increasing energy expenditure, fatty acid oxidation and locomotor activity in vivo. The decreased adiposity in HFD-Leu mice was associated with increased expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better insulin sensitivity, increased intestinal gluconeogenesis and preservation of islets of Langerhans histomorphology and function. HFD-pairfat mice had a comparable improvement in insulin sensitivity, without changes in islets physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD-pairfat mice had decreased hepatic lipid content, which likely helped improve insulin sensitivity. In contrast, when leucine was supplemented to already obese animals, no changes in body weight, body composition or glucose metabolism were observed.Conclusions/SignificanceThese findings suggest that leucine improves insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather than directly acting on peripheral target organs. However, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent type 2 diabetes development. Differently, metabolic benefit of leucine supplementation is lacking in already obese animals, a phenomenon possibly related to the extent of the obesity before starting the supplementation.

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

“…Beneficial effects on lean body mass and/or muscle mass in rats (11) and humans (7,24) have also been reported with supplementation of leucineenriched amino acid mixtures. A reduction in body fat mass has been reported with long-term leucine supplementation in animals fed a high-fat diet (6,91), during food restriction (27), and in aging rats (81), but these findings have not been confirmed in humans (7,24,80). Whether the reduction in fat gain in the current study involves differences in energy expenditure or fatty acid metabolism, as has been reported in leucine supplementation studies in rodents (6,91), is not known but is at least in part attributable to the increased utilization of amino acids for protein synthesis in muscle.…”

“…A reduction in body fat mass has been reported with long-term leucine supplementation in animals fed a high-fat diet (6,91), during food restriction (27), and in aging rats (81), but these findings have not been confirmed in humans (7,24,80). Whether the reduction in fat gain in the current study involves differences in energy expenditure or fatty acid metabolism, as has been reported in leucine supplementation studies in rodents (6,91), is not known but is at least in part attributable to the increased utilization of amino acids for protein synthesis in muscle. Moreover, these results do not support the purported causative link between increased circulating branched-chain amino acids and obesity or insulin resistance (61) but instead suggest a positive impact of leucine supplementation on body composition in growing animals.…”

In <i>Silico</i> investigation for hemoglobin characterizations leads to new aspects in susceptibility to glycosylation

“…Due to the conserved sequences it could be conjectured that the least mutation had occurred in these kinds of AA for mentioned species or some aa because had eliminated by mutations that resided these conserved sequences for hemoglobin subsequently. On the base of conserved sequence Leu has major contribution than others, so that according to the Binder et al, 2013, beneficial effects of leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might help prevent diabetes type II (Binder et al, 2013). Meanwhile, on the base of Figure 1 a lot of AAs are conserved for alpha and beta subunit of hemoglobin separately in mentioned species, so this indicates that the least mutation has occurred in hemoglobin structure after divergence of species.…”

Restrição calórica e suplementação com leucina no destreinamento físico: parâmetros lipídicos e de sensibilidade à insulina no fígado

“…Estudos tem demonstrado que a suplementação de leucina proporciona benefícios ao organismo como mudanças na composição corporal, no metabolismo da glicose e dos lipídios (BINDER et al, 2013;DUAN et al, 2015;PETZ;KLAUS, 2014;MACOTELA et al, 2011).…”

“…Dentre os BCAA, a suplementação isolada com leucina tem demonstrado resultados no que condiz com a perda de peso, melhora da sensibilidade à insulina e do perfil lipídico ZEMEL, 2011;LI et al, 2012), por atuar na regulação do metabolismo e equilíbrio energético, afetando diretamente os tecidos periféricos, tais como o tecido adiposo branco (TAB), músculos e fígado. No entanto, o efeito direto da leucina na sinalização hepática e os mecanismos associados ainda não são totalmente compreendidos (BINDER et al, 2013;LU et al, 2013;PÁDUA et al, 2009;PEDROSA et al, 2010).…”