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The role of leucine and its metabolites in protein and energy metabolism

Abstract

Leucine (Leu) is a nutritionally essential branched-chain amino acid (BCAA) in animal nutrition. It is usually one of the most abundant amino acids in high-quality protein foods. Leu increases protein synthesis through activation of the mammalian target of rapamycin (mTOR) signaling pathway in skeletal muscle, adipose tissue and placental cells. Leu promotes energy metabolism (glucose uptake, mitochondrial biogenesis, and fatty acid oxidation) to provide energy for protein synthesis, while inhibiting protein degradation. Approximately 80 % of Leu is normally used for protein synthesis, while the remainder is converted to α-ketoisocaproate (α-KIC) and β-hydroxy-β-methylbutyrate (HMB) in skeletal muscle. Therefore, it has been hypothesized that some of the functions of Leu are modulated by its metabolites. Both α-KIC and HMB have recently received considerable attention as nutritional supplements used to increase protein synthesis, inhibit protein degradation, and regulate energy homeostasis in a variety of in vitro and in vivo models. Leu and its metabolites hold great promise to enhance the growth and health of animals (including humans, birds and fish).

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Abbreviations

α-KG:

α-Ketoglutarate

α-KIC:

α-Ketoisocaproate

4E-BP1:

4E-binding protein 1

AMPK:

AMP-activated protein kinase

ATP:

Adenosine triphosphate

BCAA:

Branched-chain amino acid

BCAT:

Branched-chain amino-acid aminotransferase

BCKD:

Branched-chain α-keto acid dehydrogenase

eIF2α:

Eukaryotic initiation factor 2α

eIF4E:

Eukaryotic initiation factor 4E

eIF4G:

Eukaryotic initiation factor-4G

FFA:

Free fatty acid

GDH:

Glutamate dehydrogenase

HMB:

β-Hydroxy-β-methylbutyrate

HMG-CoA:

β-Hydroxy-β-methylglutaryl-CoA

IGF-I:

Insulin-like growth factor I

IVA-CoA:

Isovaleryl CoA

KICD:

KIC dioxygenase

KICSIS:

KIC-stimulated insulin secretion

LSIS:

Leucine-stimulated insulin secretion

MAFbx:

Muscle atrophy F-box

MAPK:

Mitogen-activated protein kinase

mTOR:

Mammalian target of rapamycin

mTORC1:

Mammalian target of rapamycin complex 1

MuRF1:

Muscle ring finger 1

NF-κB:

Nuclear factor-κB

PI3K:

Phosphoinositide-3-OH kinase

PKC:

Protein kinase C

ROS:

Reactive oxygen species

S6K1:

p70 ribosomal protein S6 kinase

SIRT1:

Silent information regulator transcript 1

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Acknowledgments

This study was jointly supported by National Basic Research Program of China (2013CB127305, 2012CB124704), National Nature Science Foundation of China (31110103909, 31330075), The Chinese Academy of Science STS Project (KFJ-EW-STS-063), Key Projects in the National Science & Technology Pillar Program (2013BAD21B04), the Hubei Hundred Talent program, and Texas A&M AgriLife Research (H-8200).

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Correspondence to Fengna Li or Yulong Yin.

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Duan, Y., Li, F., Li, Y. et al. The role of leucine and its metabolites in protein and energy metabolism. Amino Acids 48, 41–51 (2016). https://doi.org/10.1007/s00726-015-2067-1

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Keywords

  • Leucine
  • α-Ketoisocaproate
  • β-Hydroxy-β-methylbutyrate
  • Protein metabolism
  • Energy homeostasis
  • Pigs