Abstract
Leucine is an essential nutrient with potent abilities to stimulate both muscle protein synthesis as well as increased oxidative metabolism supported by mitochondrial biogenesis. Few studies have simultaneously investigated anabolic and catabolic responses following leucine treatment with the exception of master regulator of cellular energetics, AMPK. The unique ability of leucine to stimulate both favorable anabolic and catabolic processes in highly metabolically active tissues suggests leucine consumption/supplementation may provide benefits beyond hypertrophic gains. This review highlights original investigations reporting leucine’s ability to stimulate both anabolic and catabolic processes in muscle. Additionally, this report discusses potential explanations for the simultaneous activation of two seemingly opposing processes, as well as the interplay between them. The role of cellular energetics is of undeniable importance in sustaining increased protein synthesis following leucine administration; however, the dependence of leucine-induced mitochondrial biogenesis on heightened energy expenditure from elevated protein synthesis remains to be defined experimentally.
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Abbreviations
- 4E-BP1:
-
Eukaryotic translation initiation factor 4E-binding protein 1
- AA:
-
Amino acid
- ACC:
-
Acetyl-CoA carboxylase
- ACOX1:
-
Acyl-CoA oxidase 1, palmitoyl
- Akt/PKB:
-
Protein kinase B
- AMPK:
-
5′ Adenosine monophosphate-activated protein kinase
- AS160:
-
Akt substrate of 160 kDa
- ATF4:
-
Activating transcription factor 4
- CAMKII:
-
Calcium/calmodulin-dependent protein kinase II
- CKD:
-
Chronic kidney disease
- COX:
-
Cytochrome C oxidase subunit
- CPT-1B:
-
Carnitine palmitoyltransferase 1
- CrAT:
-
Carnitine O-acetyltransferase
- CRP:
-
C-reactive protein
- CytC:
-
Cytochrome C
- EDL:
-
Extensor digitorum longus
- EE:
-
Energy expenditure
- eEF:
-
Eukaryotic translation elongation factor
- eIF:
-
Eukaryotic translation initiation factor
- ERK:
-
Extracellular signal-regulated kinase
- F:
-
Female
- FAS:
-
Fatty acid synthase
- FFA:
-
Free fatty acid
- FOXO1/3a:
-
Forkhead box O1/O3a
- GβL:
-
G protein beta subunit-like
- GCN2:
-
General control nonderepressible 2
- GHR:
-
Growth hormone receptor
- GLUT4:
-
Glucose transporter 4
- GS:
-
Glycogen synthase
- GSH/GSSG:
-
Glutathione
- GSK3:
-
Glycogen synthase kinase 3
- HbA1c:
-
Glycated hemoglobin
- HOMAIR:
-
Homeostatic model assessment of insulin resistance
- Hspd1:
-
Heat shock 60 kDa protein 1
- hVps34:
-
Human vacuolar protein sorting 34
- IGF-1:
-
Insulin-like growth factor 1
- IGFBP:
-
Insulin-like growth factor-binding protein
- IL-1β/6/15:
-
Interleukin-1β/6/15
- IR:
-
Insulin receptor
- IRS1:
-
Insulin receptor substrate 1
- LAT1:
-
Large neutral amino acid transporter
- LC3I/II:
-
Microtubule-associated protein 1A/1B-light chain 3 I/II
- M:
-
Male
- MAFbx:
-
Muscle atrophy F-box
- MAPK:
-
Mitogen-activated protein kinase
- MCAD:
-
Medium-chain acyl-CoA dehydrogenase
- MCP1:
-
Monocyte chemotactic protein 1
- MDA:
-
Malondialdehyde
- MHCII:
-
Major histocompatibility complex class II
- Mnk1:
-
MAP kinase-interacting serine/threonine-protein kinase 1
- MnSOD:
-
Mitochondrial antioxidant manganese superoxide dismutase
- mTOR:
-
Mammalian target of rapamycin
- MuRF1:
-
Muscle RING finger 1
- MAPK:
-
Mitogen-activated protein kinase
- NAMPT:
-
Nicotinamide phosphoribosyltransferase
- NO:
-
Nitric oxide
- NRF:
-
Nuclear respiratory factor
- OCR:
-
Oxygen consumption rate
- PCr:
-
Creatine phosphate
- PDK:
-
Phosphoinositide-dependent kinase
- PGC-1α:
-
PPAR-gamma coactivator-1 alpha
- PI3K:
-
Phosphatidylinositol-4,5-bisphosphate 3-kinase
- PIP2:
-
Phosphatidylinositol-4,5-bisphosphate
- PIP3:
-
Phosphatidylinositol-3,4,5-trisphosphate
- PP2A:
-
Protein phosphatase 2
- PPAR:
-
Peroxisome proliferator-activator receptor
- PSMB7:
-
Proteasome subunit beta type-7
- PRAS40:
-
Proline-rich Akt substrate of 40 kDa
- REDD2:
-
Regulated in development and DNA damage responses 2
- RER:
-
Respiratory exchange ratio
- Rheb:
-
Ras-homolog enriched in the brain
- RG:
-
Red gastrocnemius
- RQ:
-
Respiratory quotient
- S6:
-
Ribosomal protein 6
- S6K:
-
Ribosomal S6 kinase
- SD:
-
Sprague-Dawley
- SIRT:
-
Sirtuin
- SNAT2:
-
Sodium-coupled neutral amino acid transporter 2
- T3:
-
Thyroid hormone 3,5,3′-triiodothyronine
- TFAM:
-
Mitochondrial transcription factor A
- TG:
-
Triglyceride
- TNFα:
-
Tumor necrosis factor alpha
- TSC:
-
Tuberous sclerosis
- UBE2K:
-
Ubiquitin-conjugating enzyme E2K
- UCHL1:
-
Ubiquitin carboxy-terminal hydrolase L1
- UCP:
-
Uncoupling protein
- ULK1:
-
Unc-51 like autophagy activating kinase 1
- WG:
-
White gastrocnemius
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Gannon, N.P., Vaughan, R.A. Leucine-induced anabolic-catabolism: two sides of the same coin. Amino Acids 48, 321–336 (2016). https://doi.org/10.1007/s00726-015-2109-8
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DOI: https://doi.org/10.1007/s00726-015-2109-8