Dose-dependent increases in p70S6K phosphorylation and intramuscular branched-chain amino acids in older men following resistance exercise and protein intake

Leucine, isoleucine and valine (i.e., the branched chain amino acids, BCAA) play a key role in the support of tissue protein regulation and can be mobilized as energy substrates during times of starvation. However, positive relationships exist between elevated levels of BCAA and insulin resistance (IR). Thus, we sought to investigate the links between fasting plasma BCAA following a progressive resistance exercise training (RET) programme, an intervention known to improve metabolic health. Fasting plasma BCAA were quantified in adults (young: 18–28 y, n = 8; middle-aged: 45–55 y, n = 9; older: 65–75 y, n = 15; BMI: 23–28 kg/m2, both males and females (~50:50), in a cross-sectional, intervention study. Participants underwent 20-weeks whole-body RET. Measurements of body composition, muscle strength (1-RM) and metabolic health biomarkers (e.g., HOMA-IR) were made at baseline and post-RET. BCAA concentrations were determined by gas-chromatography mass spectrometry (GC-MS). No associations were observed across age with BCAA; however, RET elicited (p < 0.05) increases in plasma BCAA (all age-groups), while HOMA-IR scores reduced (p < 0.05) following RET. After RET, positive correlations in lean body mass (p = 0.007) and strength gains (p = 0.001) with fasting BCAA levels were observed. Elevated BCAA are not a robust marker of ageing nor IR in those with a healthy BMI; rather, despite decreasing IR, RET was associated with increased BCAA.

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Altered Dairy Protein Intake Does Not Alter Circulatory Branched Chain Amino Acids in Healthy Adults: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu10101510 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1510 ◽

Cited By ~ 9

Author(s):

Utpal Prodhan ◽

Amber Milan ◽

Eric Thorstensen ◽

Matthew Barnett ◽

Ralph Stewart ◽

...

Keyword(s):

Amino Acids ◽

Insulin Sensitivity ◽

Protein Intake ◽

Branched Chain Amino Acids ◽

Healthy Adults ◽

Model Assessment ◽

Dairy Intake ◽

Branched Chain ◽

Dairy Protein ◽

The Impact

Dairy, as a major component of a high protein diet, is a critical dietary source of branched chain amino acids (BCAA), which are biomarkers of health and diseases. While BCAA are known to be key stimulators of protein synthesis, elevated circulatory BCAA is an independent risk factor for type 2 diabetes mellitus. This study examined the impact of altered dairy intake on plasma BCAA and their potential relationship to insulin sensitivity. Healthy adults (n = 102) were randomized to receive dietary advice to reduce, maintain, or increase habitual dairy intake for 1 month. Food intake was recorded with food frequency questionnaires. Self-reported protein intake from dairy was reported to be reduced (−14.6 ± 3.0 g/day), maintained (−4.0 ± 2.0 g/day) or increased (+13.8 ± 4.1 g/day) according to group allocation. No significant alterations in circulating free amino acids (AA), including BCAA, were measured. Insulin sensitivity, as assessed by homeostatic model assessment-insulin resistance (HOMA-IR), was also unaltered. A significant change in dairy protein intake showed no significant effect on fasting circulatory BCAA and insulin sensitivity in healthy populations.

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Associations of Fat and Lean Body Mass with Circulating Amino Acids in Older Men and Women

The Journals of Gerontology Series A ◽

10.1093/gerona/glz126 ◽

2019 ◽

Vol 75 (5) ◽

pp. 885-891 ◽

Cited By ~ 4

Author(s):

Tuija M Mikkola ◽

Minna K Salonen ◽

Eero Kajantie ◽

Hannu Kautiainen ◽

Johan G Eriksson

Keyword(s):

Amino Acids ◽

Body Composition ◽

Lean Body Mass ◽

Fat Mass ◽

Lean Mass ◽

Older Men ◽

Branched Chain Amino Acids ◽

Men And Women ◽

Branched Chain ◽

Older Men And Women

Abstract Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62–74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking, and fasting glucose. Higher lean mass index (LMI) was associated with higher concentrations of branched-chain amino acids in both sexes (p ≤ .001). In men, LMI was also positively associated with tyrosine (p = .006) and inversely with glycine (p < .001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p ≤ .008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.

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Metabolic Effects of Branched-Chain Amino Acids and Keto Acids: Mechanisms Independent of Protein Intake?

Journal of Renal Nutrition ◽

10.1053/j.jrn.2009.06.006 ◽

2009 ◽

Vol 19 (5) ◽

pp. S25-S26

Author(s):

Gábor Zakar

Keyword(s):

Amino Acids ◽

Protein Intake ◽

Branched Chain Amino Acids ◽

Metabolic Effects ◽

Keto Acids ◽

Branched Chain

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Branched-chain amino acids increase p70S6k phosphorylation in human skeletal muscle after resistance exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00430.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. E1-E7 ◽

Cited By ~ 166

Author(s):

Håkan K. R. Karlsson ◽

Per-Anders Nilsson ◽

Johnny Nilsson ◽

Alexander V. Chibalin ◽

Juleen R. Zierath ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Protein Kinase ◽

Resistance Exercise ◽

P38 Mapk ◽

Recovery Period ◽

Plasma Concentrations ◽

Branched Chain Amino Acids ◽

Mitogen Activated Protein Kinase ◽

Branched Chain

The aim of the study was to investigate the effect of resistance exercise alone or in combination with oral intake of branched-chain amino acids (BCAA) on phosphorylation of the 70-kDa S6 protein kinase (p70S6k) and mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and p38 MAPK in skeletal muscle. Seven male subjects performed one session of quadriceps muscle resistance training (4 × 10 repetitions at 80% of one repetition maximum) on two occasions. In a randomized order, double-blind, crossover test, subjects ingested a solution of BCAA or placebo during and after exercise. Ingestion of BCAA increased plasma concentrations of isoleucine, leucine, and valine during exercise and throughout recovery after exercise (2 h postexercise), whereas no change was noted after the placebo trial. Resistance exercise led to a robust increase in p70S6k phosphorylation at Ser424 and/or Thr421, which persisted 1 and 2 h after exercise. BCAA ingestion further enhanced p70S6k phosphorylation 3.5-fold during recovery. p70S6k phosphorylation at Thr389 was unaltered directly after resistance exercise. However, during recovery, Thr389 phosphorylation was profoundly increased, but only during the BCAA trial. Furthermore, phosphorylation of the ribosomal protein S6 was also increased in the recovery period only during the BCAA trial. Exercise led to a marked increase in ERK1/2 and p38 MAPK phosphorylation, which was completely suppressed upon recovery and unaltered by BCAA. In conclusion, BCAA, ingested during and after resistance exercise, mediate signal transduction through p70S6k in skeletal muscle.

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Protein intake, branched-chain amino acids, insulin release and growth in 6- to 12-month-old breast- and formula-fed infants

Acta Paediatrica ◽

10.1111/j.1651-2227.2005.tb02138.x ◽

2007 ◽

Vol 94 ◽

pp. 52a-52

Author(s):

P Karlsland Åkeson ◽

N Räihä ◽

I Axelsson

Keyword(s):

Amino Acids ◽

Insulin Release ◽

Protein Intake ◽

Branched Chain Amino Acids ◽

Branched Chain

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Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

Metabolites ◽

10.3390/metabo11060392 ◽

2021 ◽

Vol 11 (6) ◽

pp. 392

Author(s):

Ueli Bütikofer ◽

David Burnand ◽

Reto Portmann ◽

Carola Blaser ◽

Flurina Schwander ◽

...

Keyword(s):

Amino Acids ◽

Branched Chain Amino Acids ◽

Normal Weight ◽

Dependent Manner ◽

Metabolic Dysfunction ◽

High Fat ◽

Randomized Controlled ◽

Two Factors ◽

Branched Chain ◽

Dose Dependent

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity.

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Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00353.2011 ◽

2012 ◽

Vol 302 (5) ◽

pp. E510-E521 ◽

Cited By ~ 49

Author(s):

Marcus Borgenvik ◽

William Apró ◽

Eva Blomstrand

Keyword(s):

Amino Acids ◽

Resistance Exercise ◽

Total Protein ◽

Muscle Protein ◽

Recovery Period ◽

Branched Chain Amino Acids ◽

Vastus Lateralis Muscle ◽

Early Recovery ◽

Placebo Condition ◽

Branched Chain

Resistance exercise and amino acids are two major factors that influence muscle protein turnover. Here, we examined the effects of resistance exercise and branched-chain amino acids (BCAA), individually and in combination, on the expression of anabolic and catabolic genes in human skeletal muscle. Seven subjects performed two sessions of unilateral leg press exercise with randomized supplementation with BCAA or flavored water. Biopsies were collected from the vastus lateralis muscle of both the resting and exercising legs before and repeatedly after exercise to determine levels of mRNA, protein phosphorylation, and amino acid concentrations. Intake of BCAA reduced ( P < 0.05) MAFbx mRNA by 30 and 50% in the resting and exercising legs, respectively. The level of MuRF-1 mRNA was elevated ( P < 0.05) in the exercising leg two- and threefold under the placebo and BCAA conditions, respectively, whereas MuRF-1 total protein increased by 20% ( P < 0.05) only in the placebo condition. Phosphorylation of p70S6k increased to a larger extent (∼2-fold; P < 0.05) in the early recovery period with BCAA supplementation, whereas the expression of genes regulating mTOR activity was not influenced by BCAA. Muscle levels of phenylalanine and tyrosine were reduced (13–17%) throughout recovery ( P < 0.05) in the placebo condition and to a greater extent (32–43%; P < 0.05) following BCAA supplementation in both resting and exercising muscle. In conclusion, BCAA ingestion reduced MAFbx mRNA and prevented the exercise-induced increase in MuRF-1 total protein in both resting and exercising leg. Further-more, resistance exercise differently influenced MAFbx and MuRF-1 mRNA expression, suggesting both common and divergent regulation of these two ubiquitin ligases.

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