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An Update on Protein, Leucine, Omega-3 Fatty Acids, and Vitamin D in the Prevention and Treatment of Sarcopenia and Functional Decline.
Tessier, AJ, Chevalier, S
Nutrients. 2018;(8)
Abstract
Aging is associated with sarcopenia and functional decline, leading to frailty and disability. As a modifiable risk factor, nutrition may represent a target for preventing or postponing the onset of these geriatric conditions. Among nutrients, high-quality protein, leucine, vitamin D, and omega-3 polyunsaturated fatty acids (n-3 PUFA) are of particular interest for their demonstrated effects on skeletal muscle health. This narrative review aims to examine the recent observational and interventional evidence on the associations and the role of these nutrients in the muscle mass, strength, mobility, and physical function of free-living older adults, who are either healthy or at risk of frailty. Recent evidence supports a higher protein intake recommendation of 1.0⁻1.2 g/kg/day in healthy older adults; an evenly distributed mealtime protein intake or minimal protein per meal may be beneficial. In addition, vitamin D supplementation of 800⁻1000 IU, particularly when vitamin D status is low, and doses of ~3 g/day of n-3 PUFA may be favorable for physical function, muscle mass, and strength. Reviewed studies are highly heterogenous, yet the quantity, quality, and timing of intakes should be considered when designing intervention studies. Combined protein, leucine, vitamin D, and n-3 PUFA supplements may convey added benefits and may represent an intervention strategy in the prevention of sarcopenia and functional decline.
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Whi2 signals low leucine availability to halt yeast growth and cell death.
Teng, X, Yau, E, Sing, C, Hardwick, JM
FEMS yeast research. 2018;(8)
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Abstract
Cells are exquisitely tuned to environmental ques. Amino acid availability is rapidly sensed, allowing cells to adjust molecular processes and implement short or long-term metabolic shifts accordingly. How levels of most individual amino acids may be sensed and subsequently signaled to inform cells of their nutrient status is largely unknown. We made the unexpected observation that small changes in the levels of specific amino acids can have a profound effect on yeast cell growth, leading to the identification of yeast Whi2 as a negative regulator of cell growth in low amino acids. Although Whi2 was originally thought to be fungi-specific, Whi2 appears to share a conserved structural domain found in a family of 25 largely uncharacterized human genes encoding the KCTD (potassium channel tetramerization domain) protein family. Insights gained from yeast Whi2 are likely to be revealing about human KCTDs, many of which have been implicated or demonstrated to cause disease when mutated. Here we report new evidence that Whi2 responds to specific amino acids in the medium, particularly low leucine levels. We also discuss the known pathways of amino acid signaling and potential points of regulation by Whi2 in nutrient signaling in yeast and mammals.
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The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.
Xu, ZR, Tan, ZJ, Zhang, Q, Gui, QF, Yang, YM
The British journal of nutrition. 2015;(1):25-34
Abstract
In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95% CI 0·50, 1·67; P< 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95% CI - 0·18, 0·54; P= 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95% CI - 0·32, 0·44; P= 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.
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Reviewing the Effects of L-Leucine Supplementation in the Regulation of Food Intake, Energy Balance, and Glucose Homeostasis.
Pedroso, JA, Zampieri, TT, Donato, J
Nutrients. 2015;(5):3914-37
Abstract
Leucine is a well-known activator of the mammalian target of rapamycin (mTOR). Because mTOR signaling regulates several aspects of metabolism, the potential of leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central leucine injection decreases food intake, this effect is not well reproduced when leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral leucine supplementation significantly affects food intake, although several studies have shown that leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of leucine supplementation in already-obese subjects. Finally, although several studies have found that leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss.
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How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs.
Alam, T, Alazmi, M, Gao, X, Arold, ST
The Biochemical journal. 2014;(3):317-29
Abstract
LD motifs (leucine-aspartic acid motifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs.
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Muscle protein anabolism in type 2 diabetes.
Bassil, MS, Gougeon, R
Current opinion in clinical nutrition and metabolic care. 2013;(1):83-8
Abstract
PURPOSE OF REVIEW Protein anabolism is abnormal in human type 2 diabetes (T2DM). We review studies of anabolic stimuli that identify potential causes. If uncorrected, and combined with aging effects, they will compromise muscle function and mass. Knowing causes can guide studies of preventive and treatment measures. RECENT FINDINGS T2DM accelerates age-related decreases in muscle mass. This could be related to insulin resistance of whole-body protein anabolism demonstrated in hyperglycemic obese men. In contrast, their protein anabolic response to hyperaminoacidemia suggested that ample amino acid administration, especially branched chain amino acids might overcome such insulin resistance. One study of chronic leucine supplementation in elderly T2DM patients did not increase muscle mass. However, they lacked sarcopenia and had adequate dietary protein intake, so may be atypical. Exercise induced similar increases in muscle protein synthesis, mass and strength in healthy and T2DM patients suggesting that physical activity might also overcome insulin resistance of protein anabolism. SUMMARY Muscle protein anabolism in T2DM is resistant to the action of insulin but perhaps not to amino acid supply or exercise. Whether leucine supplementation improves muscle mass and function in persons with T2DM (especially elderly) with reduced protein intake or muscle mass needs to be determined.
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Dietary strategies to attenuate muscle loss during recovery from injury.
Tipton, KD
Nestle Nutrition Institute workshop series. 2013;:51-61
Abstract
Injuries are an unavoidable aspect of participation in physical activity. Nutrition is important for optimal wound healing and recovery, but little information about nutritional support for injuries exists. Immediately following injury, wound healing begins with an inflammatory response. Excessive anti-inflammatory measures may impair recovery. Many injuries result in limb immobilization. Immobilization results in muscle loss due to increased periods of negative muscle protein balance from decreased basal muscle protein synthesis and resistance to anabolic stimuli, including protein ingestion. Oxidative capacity of muscle is also decreased. Nutrient and energy deficiencies should be avoided. Energy expenditure may be reduced during immobilization, but inflammation, wound healing and the energy cost of ambulation limit the reduction of energy expenditure. There is a theoretical rationale for leucine and omega-3 fatty acid supplementation to help reduce muscle atrophy. During rehabilitation and recovery from immobilization, increased activity, in particular resistance exercise will increase muscle protein synthesis and restore sensitivity to anabolic stimuli. Ample, but not excessive, protein and energy must be consumed to support muscle growth. During rehabilitation and recovery, nutritional needs are very much like those for any athlete desiring muscle growth. The most important consideration is to avoid malnutrition and to apply a risk/benefit approach.
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Monoamine transporter structure, function, dynamics, and drug discovery: a computational perspective.
Manepalli, S, Surratt, CK, Madura, JD, Nolan, TL
The AAPS journal. 2012;(4):820-31
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Abstract
With the breakthrough crystallization of the bacterial leucine transporter protein LeuT, the first available X-ray structure for the neurotransmitter/sodium symporter family, development of 3-D computational models is suddenly essential for structure-function studies on the plasmalemmal monoamine transporters (MATs). LeuT-based MAT models have been used to guide elucidation of substrate and inhibitor binding pockets, and molecular dynamics simulations using these models are providing insight into conformations involved in the substrate translocation cycle. With credible MAT models finally in hand, structure-based virtual screening for novel ligands is yielding lead compounds toward the development of new medications for psychostimulant dependence, attention deficit hyperactivity, depression, anxiety, schizophrenia, and other disorders associated with dopamine, norepinephrine, or serotonin dysregulation.
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Long-term effects of leucine supplementation on body composition.
Balage, M, Dardevet, D
Current opinion in clinical nutrition and metabolic care. 2010;(3):265-70
Abstract
PURPOSE OF REVIEW Leucine does not only serve as a substrate for protein synthesis but is also recognized as a potent signal nutrient that regulates protein metabolism. Accordingly, leucine supplementation has been suggested to develop muscle mass or prevent protein loss in several conditions characterized by muscle protein wasting. In the present review, we reported the recent results related to the effect of dietary leucine or leucine-rich amino acid mixture and proteins on whole body composition. RECENT FINDINGS Although recent studies corroborate that increasing plasma leucine concentration generally induces an increase in muscle protein synthesis, long-term dietary leucine supplementation has been poorly investigated. Chronic free leucine supplementation alone did not improve lean body or muscle mass during resistance training or in elderly, whereas it was able to limit the weight loss induced by malnutrition. Contradictory data were also reported concerning the effect of leucine supplementation for weight management in obese patients. Leucine-rich amino acid mixture or proteins appeared more efficient than leucine alone to improve muscle mass and performance, suggesting the efficacy of leucine depends nevertheless on the presence of other amino acids. SUMMARY Until now, there is no evidence that chronic leucine supplementation is efficient in promoting muscle mass or preventing protein loss during catabolic states. Further studies are required to determine the duration and nutritional conditions of long-term leucine supplementation and to establish whether such nutritional interventions can help to prevent or treat muscle loss in various pathological or physiological conditions.
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Leucine for retention of lean mass on a hypocaloric diet.
Jitomir, J, Willoughby, DS
Journal of medicinal food. 2008;(4):606-9
Abstract
As obesity rates continue to climb, there is a pressing need for novel weight loss techniques. However, the energy-restricted diets recommended for weight loss typically result in significant amounts of lean tissue loss, in addition to the desired body fat loss. Leucine, a supported anticatabolic agent, has shown promise in research at many levels. First, leucine is known to stimulate the mammalian target of rapamycin pathway, which initiates translation and protein synthesis in muscle cells. Furthermore, leucine may help to regulate blood glucose levels by promoting gluconeogenesis. Finally, several recent studies provide evidence that leucine aids in the retention of lean mass in a hypocaloric state. The aim of this paper is to review relevant leucine research in the three areas described and assess its potential as supplement for obese individuals.