Leucine induces myofibrillar protein accretion in cultured skeletal muscle through m<scp>TOR</scp> dependent and ‐independent control of myosin heavy chain m<scp>RNA</scp> levels

Haegens, Astrid; Schols, Annemie; Essen, Anon Lm; Loon, Luc J. C. van; Langen, Ramon

doi:10.1002/mnfr.201100695

Cited by 53 publications

(41 citation statements)

References 31 publications

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“…Previous work by one of the current authors using intravenous flooding dose techniques revealed anabolic effects of other EAA in our LEAA feed (i.e., valine, phenylalanine) in man (52). Nonetheless, given potent mTORc1 signaling actions attributed to LEU (3,21,25), it is speculated LEU was central. Second, we measured neither muscle protein breakdown nor whole body protein turnover; i.e., age-related differences in splanchnic metabolism (40) and insulin handling may also impact muscle and whole body responses to feeding/exercise, particularly because of the antiproteolytic effect of insulin on muscle protein breakdown (33).…”

Section: Discussionmentioning

confidence: 77%

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

Bukhari

Phillips

Wilkinson

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

123

133

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PJ. Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise. Am J Physiol Endocrinol Metab 308: E1056-E1065, 2015. First published March 31, 2015; doi:10.1152/ajpendo.00481.2014.-Dysregulated anabolic responses to nutrition/exercise may contribute to sarcopenia; however, these characteristics are poorly defined in female populations. We determined the effects of two feeding regimes in older women (66 Ϯ 2.5 yr; n ϭ 8/group): bolus whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)]. Using [ 13 C6]phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and in response to both feeding (FED) and feeding plus exercise (FED-EX; 6 ϫ 8 knee extensions at 75% 1-repetition maximum). We also quantified plasma insulin/AA concentrations, whole leg (LBF)/muscle microvascular blood flow (MBF), and muscle anabolic signaling by phosphoimmunoblotting. Plasma insulinemia and EAA/aemia were markedly greater after WP than LEAA (P Ͻ 0.001). Neither LEAA nor WP modified LBF in response to FED or FED-EX, whereas MBF increased to a similar extent in both groups only after FED-EX (P Ͻ 0.05). In response to FED, both WP and LEAA equally stimulated MPS 0 -2 h (P Ͻ 0.05), abating thereafter (0 -4 h, P Ͼ 0.05). In contrast, after FED-EX, MPS increased at 0 -2 h and remained elevated at 0 -4 h (P Ͻ 0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr 389 increased after FED-EX (2 h, P Ͻ 0.05). APS increased similarly after WP and LEAA. Older women remain subtly responsive to nutrition Ϯ exercise. Intriguingly though, bolus WP offers no trophic advantage over LEAA. skeletal muscle; blood flow; protein synthesis; aging; amino acids; exercise ILL HEALTH ASSOCIATED WITH AGING represents a major socioeconomic burden, especially given shifting demographics toward a more aged, populous world. In particular, the loss of skeletal muscle mass associated with aging, or sarcopenia, is a major clinical issue. For instance, not only are there established links between low muscle mass and all-cause mortality per se (1), but also, lower skeletal muscle mass associated with sarcopenia leads to increased frailty, risk of falls, sedentarism, poor quality of life, and prevalence of metabolic comorbidities (17, 53).The two major extrinsic influences over muscle mass are nutrition and physical activity. For example, oral intake of protein-based foods containing essential amino acids (EAA) leads to a transient (2-3 h; see Ref.2) stimulation of muscle protein synthesis (MPS) in younger men. This brief increase in MPS above postabsorptive rates serves the purpose of replenishing protein stores lost during fasting, ensuring preservation of muscle protein mass. Similarly, physical activity is a prerequisite for maintenance of a healthy muscle mass. For example, inactivity (6, 20) causes muscle atrophy by inducing "anabo...

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Section: Discussionmentioning

confidence: 77%

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

Bukhari

Phillips

Wilkinson

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

123

133

View full text Add to dashboard Cite

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“…This is associated with a decrease in MBP activity that results from interference with insulin-induced NO production in ECs. A reduced bioavailability of NO then leads to increases in phosphorylation of MLCK, Ca 2ϩ MLCK sensitization and decreased VSMC relaxation (26). In this regard, mTOR/S6K1 inhibition, as well AT 1 R and MR blockade, may improve MBP activation in response to insulin via reductions in IRS-1 and consequent increases in PI3K/Akt signaling (26,34).…”

Section: Pi3k/aktmentioning

confidence: 99%

Overnutrition, mTOR signaling, and cardiovascular diseases

Jia

Aroor

Martinez‐Lemus

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The prevalence of obesity and associated medical disorders has increased dramatically in the United States and throughout much of the world in the past decade. Obesity, induced by excess intake of carbohydrates and fats, is a major cause of Type 2 diabetes, hypertension, and the cardiorenal metabolic syndrome. There is emerging evidence that excessive nutrient intake promotes signaling through the mammalian target of rapamycin (mTOR), which, in turn, may lead to alterations of cellular metabolic signaling leading to insulin resistance and obesity-related diseases, such as diabetes, cardiovascular and kidney disease, as well as cancer. While the pivotal role of mTOR signaling in regulating metabolic stress, autophagy, and adaptive immune responses has received increasing attention, there remain many gaps in our knowledge regarding this important nutrient sensor. For example, the precise cellular signaling mechanisms linking excessive nutrient intake and enhanced mTOR signaling with increased cardiovascular and kidney disease, as well as cancer, are not well understood. In this review, we focus on the effects that the interaction between excess intake of nutrients and enhanced mTOR signaling have on the promotion of obesity-associated diseases and potential therapeutic strategies involving targeting mTOR signaling.

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“…Leucine has previously been shown to increase muscle protein synthesis through stimulation of mammalian target of rapamycin (mTOR) and Akt phosphorylation [1][2][3][4][5]. Despite this anabolic function, leucine has also been shown to promote several processes involved in catabolic metabolism including increased expression of fatty acid oxidation genes [6][7][8][9], heightened oxygen consumption [10,11], and increased mitochondrial content in both skeletal muscle and adipocytes [8,9,11,12].…”

Section: Introductionmentioning

confidence: 98%

Leucine stimulates PPARβ/δ-dependent mitochondrial biogenesis and oxidative metabolism with enhanced GLUT4 content and glucose uptake in myotubes

et al. 2016

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Leucine induces myofibrillar protein accretion in cultured skeletal muscle through mTOR dependent and ‐independent control of myosin heavy chain mRNA levels

Abstract: This study clearly demonstrates myofibrillar and not generic protein accretion in skeletal muscle following leucine supplementation, and suggests this involves pre-translational control of MyHC expression by leucine.

Cited by 53 publications

References 31 publications

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

Overnutrition, mTOR signaling, and cardiovascular diseases

Leucine stimulates PPARβ/δ-dependent mitochondrial biogenesis and oxidative metabolism with enhanced GLUT4 content and glucose uptake in myotubes

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