Dileucine-supplemented essential amino acids support whole-body anabolism after resistance exercise and serum-stimulated cell-based anabolism.
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| Názov: | Dileucine-supplemented essential amino acids support whole-body anabolism after resistance exercise and serum-stimulated cell-based anabolism. |
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| Autori: | Aguilera JA; Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada., Tinline-Goodfellow CT; Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada., Lees MJ; Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada., Kortebi I; Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada., West DWD; Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.; KITE Research Institute, Toronto Rehabilitation Institute, Toronto, ON, Canada., Sawan SA; Iovate Health Sciences International Inc, Oakville, ON, Canada., Sharma M; Iovate Health Sciences International Inc, Oakville, ON, Canada., Bashir R; Iovate Health Sciences International Inc, Oakville, ON, Canada., Barnes TM; Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, IL, USA., Ulanov AV; Roy J. Carver Biotechnology Center, University of Illinois Urbana-Champaign, Urbana, IL, USA., Burd NA; Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana, IL, USA.; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA., Moore DR; Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada. |
| Zdroj: | Journal of the International Society of Sports Nutrition [J Int Soc Sports Nutr] 2025 Dec 31; Vol. 22 (1), pp. 2590090. Date of Electronic Publication: 2025 Nov 30. |
| Spôsob vydávania: | Journal Article; Randomized Controlled Trial |
| Jazyk: | English |
| Informácie o časopise: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101234168 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-2783 (Electronic) Linking ISSN: 15502783 NLM ISO Abbreviation: J Int Soc Sports Nutr Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2022- : [Philadelphia, PA] : Taylor & Francis Original Publication: [Woodland Park, Colo.] : International Society of Sports Nutrition, [2004]- |
| Výrazy zo slovníka MeSH: | Leucine*/administration & dosage , Leucine*/pharmacology , Resistance Training* , Dietary Supplements* , Amino Acids, Essential*/administration & dosage, Humans ; Male ; Cross-Over Studies ; Double-Blind Method ; Young Adult ; Adult ; Muscle Proteins/metabolism ; Muscle Proteins/biosynthesis ; Amino Acids, Branched-Chain/administration & dosage ; Muscle, Skeletal/metabolism ; Female ; Methylhistidines/urine ; Mechanistic Target of Rapamycin Complex 1/metabolism |
| Abstrakt: | Background: Essential (EAA) and branched chain (BCAA) amino acid ingestion support whole-body anabolism after resistance exercise and can attenuate markers of postexercise myofibrillar protein breakdown (i.e. urinary 3-methylhistidine; 3MH). Leucine is often considered a primary anabolic EAA through its ability to activate the mechanistic target of rapamycin complex 1 (mTORC1) and stimulate muscle protein synthesis. The dipeptide leucine (dileucine) has been shown to more effectively stimulate myofibrillar protein synthesis than leucine in young males at rest. Therefore, we aimed to determine the effect of a dileucine-containing essential amino acid formula (DIEAA; 2 g dileucine, 1 g leucine, 9.15 g total EAA) on the anabolic and catabolic responses following resistance exercise in young recreationally active adults when compared with ingesting branched chain amino acids (BCAA; 3 g leucine, 1.5 g isoleucine, 1.5 g valine) or isonitrogenous (to DIEAA) collagen hydrolysate (COL). Methods: In a randomized, double-blind, crossover design, 12 healthy adults (8 M, 4F, aged 24 ± 3 y) performed a 60 min bout of whole-body resistance exercise, after which they ingested DIEAA, BCAA, or COL protein beverages containing 100 mg L-[1- 13 C]leucine (#NCT05754125). Total exogenous leucine retention (as an estimate of whole-body anabolism) was assessed over the 6 h postprandial period by determining total leucine oxidation from 13 CO Results: Total exogenous leucine retention were similar ( p = 0.68) between DIEAA (215.72 ± 42.45 μmol·kg -1 ) and BCAA conditions (219.15 ± 45.26 μmol·kg -1 ), with both DIEAA and BCAA being greater ( p < 0.0001) than COL (37.25 ± 8.16 μmol·kg -1 ). There were no differences ( p = 0.58) in 3MH:Cr between supplement conditions. There was no effect of condition ex vivo on puromycin incorporation into nascent peptides ( p = 0.31), total protein ubiquitination as an estimate of protein breakdown ( p = 0.59), phosphorylation of downstream mTORC1 substrates p -RPS6 S240/244 ( p = 0.39) or p -4E-BP1 T37/46 ( p = 0.50), and myotube diameter ( p = 0.55). Stable isotope-derived rates of mixed muscle protein synthesis (MPS) demonstrated a trend toward a main effect ( p = 0.086) with pairwise comparisons revealing a large effect of DIEAA compared to COL (dz = 1.47), a medium effect of DIEAA compared to BCAA (dz = 0.81), and a trivial effect of BCAA comapred to COL (dz = 0.002). Conclusions: Dileucine-supplemented EAA and BCAA support greater whole-body anabolism compared with COL after resistance exercise independent of attenuation in urinary estimates of myofibrillar protein breakdown. Exploratory ex vivo experiments reveal a potential anabolic effect of DIEAA in stimulating MPS. Collectively, these findings suggest that consuming dileucine with sufficient EAA and BCAA increases exogenous leucine retention to support whole-body anabolism during postexercise recovery in individuals performing resistance training. |
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| Contributed Indexing: | Keywords: Dileucine; essential amino acids; resistance training; supplementation; whole-body anabolism |
| Substance Nomenclature: | GMW67QNF9C (Leucine) 0 (Amino Acids, Essential) 0 (Muscle Proteins) 0 (Amino Acids, Branched-Chain) 0 (Methylhistidines) EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) MEH8O8Y0H0 (3-methylhistidine) |
| Entry Date(s): | Date Created: 20251201 Date Completed: 20251201 Latest Revision: 20251204 |
| Update Code: | 20251204 |
| PubMed Central ID: | PMC12671060 |
| DOI: | 10.1080/15502783.2025.2590090 |
| PMID: | 41321015 |
| Databáza: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Background: Essential (EAA) and branched chain (BCAA) amino acid ingestion support whole-body anabolism after resistance exercise and can attenuate markers of postexercise myofibrillar protein breakdown (i.e. urinary 3-methylhistidine; 3MH). Leucine is often considered a primary anabolic EAA through its ability to activate the mechanistic target of rapamycin complex 1 (mTORC1) and stimulate muscle protein synthesis. The dipeptide leucine (dileucine) has been shown to more effectively stimulate myofibrillar protein synthesis than leucine in young males at rest. Therefore, we aimed to determine the effect of a dileucine-containing essential amino acid formula (DIEAA; 2 g dileucine, 1 g leucine, 9.15 g total EAA) on the anabolic and catabolic responses following resistance exercise in young recreationally active adults when compared with ingesting branched chain amino acids (BCAA; 3 g leucine, 1.5 g isoleucine, 1.5 g valine) or isonitrogenous (to DIEAA) collagen hydrolysate (COL).<br />Methods: In a randomized, double-blind, crossover design, 12 healthy adults (8 M, 4F, aged 24 ± 3 y) performed a 60 min bout of whole-body resistance exercise, after which they ingested DIEAA, BCAA, or COL protein beverages containing 100 mg L-[1- <sup>13</sup> C]leucine (#NCT05754125). Total exogenous leucine retention (as an estimate of whole-body anabolism) was assessed over the 6 h postprandial period by determining total leucine oxidation from <sup>13</sup> CO <subscript>2</subscript> enrichment (isotope ratio mass spectrometry) in repeated breath samples. A urinary 3MH:creatinine ratio (3MH:Cr) over 6 h was used as an estimate of skeletal muscle myofibrillar protein breakdown. To further assess the anabolic potential of nutrients, C2C12 myotubes were treated with a subset ( n = 7) of human serum-conditioned media for 4 h to measure downstream mTORC1 substrate phosphorylation, protein synthesis (puromycin and L- ring -[D <subscript>5</subscript> ]phenylalanine incorporation) and breakdown (ubiquitinated protein), and myotube hypertrophy.<br />Results: Total exogenous leucine retention were similar ( p = 0.68) between DIEAA (215.72 ± 42.45 μmol·kg <sup>-1</sup> ) and BCAA conditions (219.15 ± 45.26 μmol·kg <sup>-1</sup> ), with both DIEAA and BCAA being greater ( p < 0.0001) than COL (37.25 ± 8.16 μmol·kg <sup>-1</sup> ). There were no differences ( p = 0.58) in 3MH:Cr between supplement conditions. There was no effect of condition ex vivo on puromycin incorporation into nascent peptides ( p = 0.31), total protein ubiquitination as an estimate of protein breakdown ( p = 0.59), phosphorylation of downstream mTORC1 substrates p -RPS6 <sup>S240/244</sup> ( p = 0.39) or p -4E-BP1 <sup>T37/46</sup> ( p = 0.50), and myotube diameter ( p = 0.55). Stable isotope-derived rates of mixed muscle protein synthesis (MPS) demonstrated a trend toward a main effect ( p = 0.086) with pairwise comparisons revealing a large effect of DIEAA compared to COL (dz = 1.47), a medium effect of DIEAA compared to BCAA (dz = 0.81), and a trivial effect of BCAA comapred to COL (dz = 0.002).<br />Conclusions: Dileucine-supplemented EAA and BCAA support greater whole-body anabolism compared with COL after resistance exercise independent of attenuation in urinary estimates of myofibrillar protein breakdown. Exploratory ex vivo experiments reveal a potential anabolic effect of DIEAA in stimulating MPS. Collectively, these findings suggest that consuming dileucine with sufficient EAA and BCAA increases exogenous leucine retention to support whole-body anabolism during postexercise recovery in individuals performing resistance training. |
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| ISSN: | 1550-2783 |
| DOI: | 10.1080/15502783.2025.2590090 |