Acute oral administration of L-leucine upregulates slow-fiber– and mitochondria-related genes in skeletal muscle of rats

Sato, Yoriko; Sato, Yusuke; Obeng, Kodwo Amuzuah; Yoshizawa, Fumiaki

doi:10.1016/j.nutres.2018.05.006

Cited by 23 publications

(27 citation statements)

References 29 publications

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“…It should be mentioned that the TFAM, Cytc and ATP5G mRNA expressions in longissimus dorsi muscle returned to as same as control level in the treatment of 0.5% leucine. Additionally, leucine supplementation has also been reported to increase ATP content and mitochondrial biogenesis in mice (Li, Xu, Lee, He, & Xie, 2012) and rats (Sato et al, 2018). Additionally, leucine supplementation has also been reported to increase ATP content and mitochondrial biogenesis in mice (Li, Xu, Lee, He, & Xie, 2012) and rats (Sato et al, 2018).…”

Section: Mammalian Cells Have a Complex Network Of Antioxidant Enzymesmentioning

confidence: 97%

“…Several transcription factors are involved in the regulation of mitochondrial biogenesis (Bhatti, Bhatti, & Reddy, 2017). The in vivo and in vitro studies showed that leucine can increase mitochondrial biogenesis (Liang, Curry, Brown, & Zemel, 2014;Sato, Sato, Obeng, & Yoshizawa, 2018;Sun & Zemel, 2009). The in vivo and in vitro studies showed that leucine can increase mitochondrial biogenesis (Liang, Curry, Brown, & Zemel, 2014;Sato, Sato, Obeng, & Yoshizawa, 2018;Sun & Zemel, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Effects of dietary leucine on antioxidant activity and expression of antioxidant and mitochondrial‐related genes in longissimus dorsi muscle and liver of piglets

Chen

Xiang

Jia

et al. 2019

Animal Science Journal

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The study was conducted to investigate the effects of dietary leucine on antioxidant activity and expression of antioxidant-and mitochondrial-related genes in longissimus dorsi muscle and liver of piglets. Three diets were formulated with different levels of supplemented leucine (0%, 0.25%, 0.5%). Results showed that supplementation of 0.25% leucine significantly increased antisuperoxide anion (ASA) and antihydroxyl radical (AHR) levels and activities of total superoxide dismutade (T-SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and total antioxidant capacity (T-AOC) in serum, longissimus dorsi muscle and liver of piglets as compared with the control group. The SOD2, catalase (CAT), GPx, GST, glutathione reductase (GR), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels in longissimus dorsi muscle and liver were significantly increased by 0.25% leucine supplementation. However, the malondialdehyde (MDA) content and the mRNA level of Kelchlike ECH-associated protein 1 (Keap1) exhibited an opposite tendency. Additionally, supplementation of 0.25% leucine significantly increased the mRNA levels of mitochondrial-related genes in longissimus dorsi muscle and liver of piglets. Results suggested that supplementation of 0.25% leucine improved antioxidant activity and mitochondrial biogenesis and function of piglets, which was related to the increase in antioxidant enzymes activities and upregulation of expression of antioxidant-and mitochondrial-related genes. K E Y W O R D S antioxidant activity, leucine, mitochondrial, piglets | 991 CHEN Et al.

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Section: Mammalian Cells Have a Complex Network Of Antioxidant Enzymesmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Effects of dietary leucine on antioxidant activity and expression of antioxidant and mitochondrial‐related genes in longissimus dorsi muscle and liver of piglets

Chen

Xiang

Jia

et al. 2019

Animal Science Journal

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“…Leucine's ability to promote Ppargc1a expression in an mTOR‐dependent fashion has been reproduced in C2C12 myotubes (Sato et al, ). Importantly , the same report also verified leucine's ability to induce Ppargc1a expression in vivo using extensor digitorum longus and soleus muscle of rats given oral leucine (Sato et al, ). Given leucine's ability to stimulate protein synthesis via mTOR, it is also conceivable that leucine may increase mitochondrial biogenesis in part through activation of mTOR.…”

Section: Introductionmentioning

confidence: 99%

“…Of the BCAA, leucine is the most heavily researched as a result of its potent ability to stimulate muscle protein synthesis through the activation of mammalian target of rapamycin (mTOR) (Deldicque et al, 2008;Du et al, 2007), the details of which are described elsewhere (Dodd and Tee, 2012). In addition to protein synthesis, leucine may also stimulate cellular metabolism and mitochondrial biogenesis in both cultured adipocytes and myotubes (Liang et al, 2014;Sato et al, 2018;Schnuck et al, 2016b;Sun and Zemel, 2009;Vaughan et al, 2013), much of which is also reviewed elsewhere (Gannon and Vaughan, 2015). Briefly, leucine activates a master regulator of cellular energetics 5 0 adenosine monophosphate-activated protein kinase (AMPK-5 0 ) that activates or upregulates the expression of multiple downstream targets including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) (Liang et al, 2014;Schnuck et al, 2016b;Sun and Zemel, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Ultimately, mTOR-mediated mitochondrial biogenesis has been attributed to the ability of mTOR to promote interactions between PGC-1α and transcription factor yin-yang 1 (YY1), as well as upregulate PGC-1α (which promotes YY1 expression), which together increase expression of mitochondrial genes (Cunningham et al, 2007). Leucine's ability to promote Ppargc1a expression in an mTOR-dependent fashion has been reproduced in C2C12 myotubes (Sato et al, 2018). Importantly, the same report also verified leucine's ability to induce Ppargc1a expression in vivo using extensor digitorum longus and soleus muscle of rats given oral leucine (Sato et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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

Johnson

Gannon

Schnuck

et al. 2018

Lipids

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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.

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Branched‐Chain Amino Acids and Mitochondrial Biogenesis: An Overview and Mechanistic Summary

Hinkle

Rivera

Vaughan

2022

Molecular Nutrition Food Res

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Branched‐chain amino acids (BCAA) are essential in the diet and promote several vital cell responses which may have benefits for health and athletic performance, as well as disease prevention. While BCAA are well‐known for their ability to stimulate muscle protein synthesis, their effects on cell energetics are also becoming well‐documented, but these receive less attention. In this review, much of the current evidence demonstrating BCAA ability (as individual amino acids or as part of dietary mixtures) to alter regulators of cellular energetics with an emphasis on mitochondrial biogenesis and related signaling is highlighted. Several studies have shown, both in vitro and in vivo, that BCAA (either individual or as a mixture) may promote signaling associated with increased mitochondrial biogenesis including the upregulation of master regulator of mitochondrial biogenesis peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), as well as numerous downstream targets and related function. However, sparse data in humans and the difficulty of controlling variables associated with feeding studies leave the physiological relevance of these findings unclear. Future well‐controlled diet studies will be needed to assess if BCAA consumption is associated with increased mitochondrial biogenesis and improved metabolic outcomes in healthy and/or diseased human populations.

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Acute oral administration of L-leucine upregulates slow-fiber– and mitochondria-related genes in skeletal muscle of rats

Cited by 23 publications

References 29 publications

Effects of dietary leucine on antioxidant activity and expression of antioxidant and mitochondrial‐related genes in longissimus dorsi muscle and liver of piglets

Effects of dietary leucine on antioxidant activity and expression of antioxidant and mitochondrial‐related genes in longissimus dorsi muscle and liver of piglets

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

Branched‐Chain Amino Acids and Mitochondrial Biogenesis: An Overview and Mechanistic Summary

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