Leucine Supplementation: A Novel Strategy for Modulating Lipid Metabolism and Energy Homeostasis

Abstract

Lipid metabolism is an important and complex biochemical process involved in the storage of energy and maintenance of normal biological functions. Leucine, a branched amino acid, has anti-obesity effects on glucose tolerance, lipid metabolism, and insulin sensitivity. Leucine also modulates mitochondrial dysfunction, representing a new strategy to target aging, neurodegenerative disease, obesity, diabetes, and cardiovascular disease. Although various studies have been carried out, much uncertainty still exists and further studies are required to fully elucidate the relationship between leucine and lipid metabolism. This review offers an up-to-date report on leucine, as key roles in both lipid metabolism and energy homeostasis in vivo and in vitro by acceleration of fatty acid oxidation, lipolysis, activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)–silent information regulator of transcription 1 (SIRT1)–proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, synthesis, and/or secretion of adipokines and stability of the gut microbiota.

The impact of acute beta-hydroxy-beta-methylbutyrate (HMB) ingestion on glucose and insulin kinetics in young and older men

“…In agreement with reports across numerous studies illustrating the positive effect of Leucine on insulin sensitivity ( Zhang et al, 2020 ), our data herein suggests that certain amino acid metabolites may also have the ability to positively modulate glucose metabolism under specific conditions. One potential mechanism that may underlie any improvement in insulin sensitivity could be an increase in leg blood flow facilitating greater peripheral glucose uptake, however this increase was not evident in this study.…”

HMB Improves Lipid Metabolism of Bama Xiang Mini-Pigs via Modulating the Bacteroidetes-Acetic Acid-AMPKα Axis

“…Leucine functions as a direct-acting nutrient signal in WAT to affect lipid metabolism, thus favoring adiposity reduction (Yao et al, 2016;Zhang et al, 2020). Despite these positive outcomes, multiple lines of evidence have pointed out that elevated levels of circulating leucine may precede or coincide with insulin resistance and cardiovascular dysfunction, thus seriously threatening human health (Felig et al, 1969;Yang et al, 2015).…”

“…The metabolic activity of the gut microbiota can be linked to host body energy homoeostasis by short-chain fatty acids (SCFAs), which are produced by gut microbiota catabolizing dietary fibers (Topping and Clifton, 2001). There is compelling evidence that nutrients can attenuate obesity by reprogramming gut microbiota (Xu et al, 2017;Yin et al, 2018;Zhang et al, 2019;Wang et al, 2020;Zhong et al, 2020). Using a rodent model, we also found that HMB could mitigate lipid metabolism disorders by reprogramming gut microbiota, as manifested by the increased ratio of Bacteroidetes to Firmicutes and elevated Bacteroidetesproduced propionic acid (Duan et al, 2019).…”

Efficacy of Dietary and Supplementation Interventions for Individuals with Type 2 Diabetes

“…Function of GLP-1 and GIP is compromised in T2D, but research suggests BCAA ingestion stimulates inhibited GLP-1 and GIP for improved insulin secretion [ 203 , 204 , 206 ]. Special consideration has been given to leucine and its metabolites due to its insulinotropic effects and stimulation of the mammalian target of rapamycin (mTOR) pathway which regulates protein synthesis, cell growth, and fuel metabolism [ 203 , 207 , 208 , 209 ]. Specifically, rapamycin-sensitive (mTORC1), a component of mTOR, is activated in response to an increase in cellular levels of leucine [ 209 , 210 ].…”

“…Special consideration has been given to leucine and its metabolites due to its insulinotropic effects and stimulation of the mammalian target of rapamycin (mTOR) pathway which regulates protein synthesis, cell growth, and fuel metabolism [ 203 , 207 , 208 , 209 ]. Specifically, rapamycin-sensitive (mTORC1), a component of mTOR, is activated in response to an increase in cellular levels of leucine [ 209 , 210 ]. This signaling pathway elicits mRNA translation and protein synthesis while decreasing muscle wasting and cell death when activated [ 208 , 211 ].…”