Leucine, Palmitate, or Leucine/Palmitate Cotreatment Enhances Myotube Lipid Content and Oxidative Preference

Abstract

Branched‐chain amino acids (BCAA) such as leucine stimulate favorable metabolic processes involved in lean tissue preservation and skeletal muscle metabolism. However, higher levels of circulating BCAA correlate with severity of metabolic disease (including diabetes/insulin resistance), and may result from dysregulated BCAA catabolism. Past observations have demonstrated potential interaction between BCAA and dietary fat; however, much of this relationship remains underexplored. This study investigated the effect of leucine both with and without palmitate on oxidative and glycolytic metabolism, as well as indicators of BCAA catabolism using cultured skeletal muscle cells. Specifically, C2C12 myotubes were treated with or without varying concentrations of leucine both with and without palmitate for 24 h. Leucine treatment significantly elevated mRNA expression of metabolic regulators including peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha versus leucine with concurrent palmitate treatment. Interestingly, leucine‐only, palmitate‐only, and leucine with palmitate all significantly increased cellular lipid content, which translated into significantly increased oxidative capacity under substrate‐limited conditions. However, upon the addition of excess substrate and carnitine, discrepancies in peak metabolic capacities between various treatments were no longer observed, suggesting leucine, palmitate, or the combination thereof causes a shift in metabolic preference from glycolytic to oxidative. These data also suggest leucine's effect on mitochondrial metabolism may result in part from increased lipid stores in addition to other previously documented pathways.

Leucine decreases intramyocellular lipid deposition in an mTORC1-independent manner in palmitate-treated C2C12 myotubes

“…Previous in vivo research from our laboratory also showed increased expression of markers such as FAS and PPAR␥ in skeletal muscle from obese Zucker rats fed with a high-protein diet containing a high amount of leucine (12). Moreover, treatment of C2C12 myotubes with palmitate and leucine reduced the effect of leucine on regulation of Tfam and PGC1␣ (19). Here, we report upregulation of mitochondrial biogenesis-related gene expression (e.g., PGC1␣, PPAR␥, NRF1, and Tfam) and mitochondrial content observed in palmitate-treated myotubes with leucine supple-mentation.…”

“…Leucine is well known for activating the mTORC1 pathway in multiple cell types (16,19), leading to activation of the translation initiation factors, which can increase protein synthesis. In Fig.…”

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

“…In recent years, there has been great interest in the role of Leu in the metabolism of the adipose tissue [33]. It is important to emphasize that many in vitro and in vivo experiments have shown that Leu modulates lipid metabolism, mainly by inhibiting fat synthesis and decomposition, and increasing energy consumption [11,14,55]. There is growing evidence to suggest that the mitochondria may play a key role in modulating adipocyte lipid metabolism [56][57][58].…”

Optimization of Wheat Embryo Globulin Fermenting Process and Variation in Properties during Fermentation

“…Aspartate a synthetic precursor of Lysine, Threonine and other amino acids as well as purine and pyrimidine based in vivo. It could be used as an adjutant in curing heart disease, liver disease and hypertension, and was effective in relieving fatigue (Hansen and Behrman, 2016); Serine had a wide range of medical applications, functioning as fat and fatty acid metabolism boosters or serving as normal immune function maintenance (Abbas, 2017); Leucine and its metabolites had regulatory effects on nutrient metabolism, neuroendocrine regulation, gene expression, signal transduction and immune function in vivo (Johnson et al, 2018). As an essential amino acid, Lysine can help drive human development, enhanced immune function, and improved the function of central nervous tissue (Passioura et al, 2019).…”