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https://www.readbyqxmd.com/read/28127425/novel-metabolic-and-physiological-functions-of-branched-chain-amino-acids-a-review
#1
REVIEW
Shihai Zhang, Xiangfang Zeng, Man Ren, Xiangbing Mao, Shiyan Qiao
It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28115977/efficacy-of-a-novel-formulation-of-l-carnitine-creatine-and-leucine-on-lean-body-mass-and-functional-muscle-strength-in-healthy-older-adults-a-randomized-double-blind-placebo-controlled-study
#2
Malkanthi Evans, Najla Guthrie, John Pezzullo, Toran Sanli, Roger A Fielding, Aouatef Bellamine
BACKGROUND: Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary objective, we sought to assess the effect of a novel combination of L-Carnitine, creatine and leucine on muscle mass and performance in older subjects. METHOD: Forty-two healthy older adults aged 55-70 years were randomized to receive either a novel L-Carnitine (1500 mg), L-leucine (2000 mg), creatine (3000 mg), Vitamin D3 (10 μg) (L-Carnitine-combination) product (n = 14), L-Carnitine (1500 mg) (n = 14), or a placebo (n = 14) for eight weeks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28089725/high-concentration-of-branched-chain-amino-acids-promotes-oxidative-stress-inflammation-and-migration-of-human-peripheral-blood-mononuclear-cells-via-mtorc1-activation
#3
Olha Zhenyukh, Esther Civantos, Marta Ruiz-Ortega, Maria Soledad Sánchez, Clotilde Vázquez, Concepción Peiró, Jesús Egido, Sebastián Mas
Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors...
January 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28017449/anabolic-resistance-does-not-explain-sarcopenia-in-patients-with-type-2-diabetes-mellitus-compared-with-healthy-controls-despite-reduced-mtor-pathway-activity
#4
Daniel J Cuthbertson, John Babraj, Graham Leese, Mario Siervo
BACKGROUND: Ageing and type 2 diabetes mellitus (T2DM) are risk factors for skeletal muscle loss. We investigated whether anabolic resistance to feeding might underlie accelerated muscle loss in older people with T2DM and whether dysregulated mTOR signalling was implicated. SUBJECTS: 8 obese men with T2DM, and 12 age-matched controls were studied (age 68 ± 3 vs. 68±6 y; BMI: 30 ± 2 vs. 27 ± 5 kg m(-2)). METHODS: Body composition was measured by dual-X-ray absorptiometry...
November 25, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27988363/in-vitro-antiglioma-action-of-indomethacin-is-mediated-via-amp-activated-protein-kinase-mtor-complex-1-signalling-pathway
#5
Aleksandar Pantovic, Mihajlo Bosnjak, Katarina Arsikin, Milica Kosic, Milos Mandic, Biljana Ristic, Jelena Tosic, Danica Grujicic, Aleksandra Isakovic, Nikola Micic, Vladimir Trajkovic, Ljubica Harhaji-Trajkovic
We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis...
December 14, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27951586/nlrc3-is-an-inhibitory-sensor-of-pi3k-mtor-pathways-in-cancer
#6
Rajendra Karki, Si Ming Man, R K Subbarao Malireddi, Sannula Kesavardhana, Qifan Zhu, Amanda R Burton, Bhesh Raj Sharma, Xiaopeng Qi, Stephane Pelletier, Peter Vogel, Philip Rosenstiel, Thirumala-Devi Kanneganti
NLRs (nucleotide-binding domain and leucine-rich repeats) belong to a large family of cytoplasmic sensors that regulate an extraordinarily diverse range of biological functions. One of these functions is to contribute to immunity against infectious diseases, but dysregulation of their functional activity leads to the development of inflammatory and autoimmune diseases. Cytoplasmic innate immune sensors, including NLRs, are central regulators of intestinal homeostasis. NLRC3 (also known as CLR16.2 or NOD3) is a poorly characterized member of the NLR family and was identified in a genomic screen for genes encoding proteins bearing leucine-rich repeats (LRRs) and nucleotide-binding domains...
December 12, 2016: Nature
https://www.readbyqxmd.com/read/27938033/long-term-leucine-supplementation-improves-metabolic-but-not-molecular-responses-in-the-skeletal-muscle-of-trained-rats-submitted-to-exhaustive-exercise
#7
Gustavo Barbosa Dos Santos, André Gustavo de Oliveira, Maria Cristina Cintra Gomes Marcondes, Miguel Arcanjo Areas
AIM: Although there is some evidence of an ergogenic effect of leucine supplementation on acute response to exercise, there is a paucity of information on whether long-term leucine supplementation influences the adaptive response to chronic endurance training and performance. The main aim of our study was to assess the role of long-term leucine supplementation on molecular and metabolic response in skeletal muscle of trained rats after an exhaustion test. METHODS: Twenty-four male Wistar rats were randomly allocated into 4 groups...
February 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/27915972/resistance-to-cell-death-and-its-modulation-in-cancer-stem-cells
#8
Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27824141/nesfatin-1-promotes-brown-adipocyte-phenotype
#9
Yuexin Wang, Ziru Li, Xinyu Zhang, Xinxin Xiang, Yin Li, Michael W Mulholland, Weizhen Zhang
Nesfatin-1, an 82 amino acid gastric peptide, is involved in regulation of food uptake and in multiple metabolic activities. Whether nesfatin-1 modulates the differentiation and lipid metabolism of brown adipocytes remains unknown. In the present study, we found that nesfatin-1 mRNA and protein were detectable in isolated brown adipocytes and gradually decreased during differentiation (95% CI 0.6057 to 1.034, p = 0.0001). The decrease in nesfatin-1 was associated with a significant reduction in p-S6. Exposure to nesfatin-1 promoted differentiation of brown adipocytes as revealed by a significant increase in UCP1 mRNA (p = 0...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27731364/mtor-independent-regulation-of-macroautophagy-by-leucine-rich-repeat-kinase-2-via-beclin-1
#10
Claudia Manzoni, Adamantios Mamais, Dorien A Roosen, Sybille Dihanich, Marc P M Soutar, Helene Plun-Favreau, Rina Bandopadhyay, John Hardy, Sharon A Tooze, Mark R Cookson, Patrick A Lewis
Leucine rich repeat kinase 2 is a complex enzyme with both kinase and GTPase activities, closely linked to the pathogenesis of several human disorders including Parkinson's disease, Crohn's disease, leprosy and cancer. LRRK2 has been implicated in numerous cellular processes; however its physiological function remains unclear. Recent reports suggest that LRRK2 can act to regulate the cellular catabolic process of macroautophagy, although the precise mechanism whereby this occurs has not been identified. To investigate the signalling events through which LRRK2 acts to influence macroautophagy, the mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) and Beclin-1/phosphatidylinositol 3-kinase (PI3K) pathways were evaluated in astrocytic cell models in the presence and absence of LRRK2 kinase inhibitors...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27716121/leucine-rich-diet-alters-the-1-h-nmr-based-metabolomic-profile-without-changing-the-walker-256-tumour-mass-in-rats
#11
Laís Rosa Viana, Rafael Canevarolo, Anna Caroline Perina Luiz, Raquel Frias Soares, Camila Lubaczeuski, Ana Carolina de Mattos Zeri, Maria Cristina Cintra Gomes-Marcondes
BACKGROUND: Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia)...
October 3, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27696482/prostate-cancer-cells-in-different-androgen-receptor-status-employ-different-leucine-transporters
#12
Hideo Otsuki, Toru Kimura, Takashi Yamaga, Takeo Kosaka, Jun-Ichi Suehiro, Hiroyuki Sakurai
BACKGROUND: Leucine stimulates cancer cell proliferation through the mTOR pathway, therefore, inhibiting leucine transporters may be a novel therapeutic target for cancer. L-type amino acid transporter (LAT) 1, a Na(+) -independent amino acid transporter, is highly expressed in many tumor cells. However, leucine transporter(s) in different stages of prostate cancer, particularly in the stages of castration resistance with androgen receptor (AR) expression, is unclear. METHODS: LNCaP and DU145 and PC-3 cell lines were used as a model of androgen dependent, and metastatic prostate cancer...
February 2017: Prostate
https://www.readbyqxmd.com/read/27690010/recent-advances-in-understanding-amino-acid-sensing-mechanisms-that-regulate-mtorc1
#13
Liufeng Zheng, Wei Zhang, Yuanfei Zhou, Fengna Li, Hongkui Wei, Jian Peng
The mammalian target of rapamycin (mTOR) is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs), especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27640900/dietary-interventions-that-reduce-mtor-activity-rescue-autistic-like-behavioral-deficits-in-mice
#14
Jiangbo Wu, Caroline G M de Theije, Sofia Lopes da Silva, Suzanne Abbring, Hilma van der Horst, Laus M Broersen, Linette Willemsen, Martien Kas, Johan Garssen, Aletta D Kraneveld
Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs...
January 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27617277/the-akt-mtor-pathway-data-comparing-young-and-aged-mice-with-leucine-supplementation-at-the-onset-of-skeletal-muscle-regeneration
#15
Richard A Perry, Lemuel A Brown, David E Lee, Jacob L Brown, Jamie I Baum, Nicholas P Greene, Tyrone A Washington
The data described herein is related to the article "Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration" [1]. Aging is associated with a decreased ability of skeletal muscle to regenerate following injury. Leucine supplementation has been extensively shown, in young subjects, to promote protein synthesis during regeneration; however, the effects of leucine supplementation on the Akt/mTOR pathway in aged mice at the onset of muscle regeneration are not fully elucidated...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27611972/activation-of-cannabinoid-receptor-2-ameliorates-dss-induced-colitis-through-inhibiting-nlrp3-inflammasome-in-macrophages
#16
Ping Ke, Bo-Zong Shao, Zhe-Qi Xu, Wei Wei, Bin-Ze Han, Xiong-Wen Chen, Ding-Feng Su, Chong Liu
Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1)...
2016: PloS One
https://www.readbyqxmd.com/read/27490818/branched-chain-amino-acids-as-new-biomarkers-of-major-depression-a-novel-neurobiology-of-mood-disorder
#17
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Hans-Bernd Rothenhäusler, Simon Theokas, Christoph Robier, Harald Mangge, Gerhard Reicht, Peter Hlade, Andreas Meinitzer
BACKGROUND: The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression. METHODS: The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography...
2016: PloS One
https://www.readbyqxmd.com/read/27477288/leucyl-trna-synthetase-activates-vps34-in-amino-acid-sensing-mtorc1-signaling
#18
Mee-Sup Yoon, Kook Son, Edwin Arauz, Jung Min Han, Sunghoon Kim, Jie Chen
Amino acid availability activates signaling by the mammalian target of rapamycin (mTOR) complex 1, mTORC1, a master regulator of cell growth. The class III PI-3-kinase Vps34 mediates amino acid signaling to mTORC1 by regulating lysosomal translocation and activation of the phospholipase PLD1. Here, we identify leucyl-tRNA synthetase (LRS) as a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS is necessary for amino acid-induced Vps34 activation, cellular PI(3)P level increase, PLD1 activation, and PLD1 lysosomal translocation...
August 9, 2016: Cell Reports
https://www.readbyqxmd.com/read/27465934/efficacy-of-system-l-amino-acid-transporter-1-inhibition-as-a-therapeutic-target-in-esophageal-squamous-cell-carcinoma
#19
Yasuhiro Ohshima, Kyoichi Kaira, Aiko Yamaguchi, Noboru Oriuchi, Hideyuki Tominaga, Shushi Nagamori, Yoshikatsu Kanai, Takehiko Yokobori, Tatsuya Miyazaki, Takayuki Asao, Yoshito Tsushima, Hiroyuki Kuwano, Noriko S Ishioka
System l amino acid transporter 1 (LAT1) is highly expressed in various types of human cancer, and contributes to cancer growth and survival. Recently, we have shown that LAT1 expression is closely related to the growth and aggressiveness of esophageal cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal cancer growth. In this study, we investigated the tumor-suppressive effects of the inhibition of LAT1. Both LAT1 and CD98, which covalently associates to LAT1 on the membrane, were expressed in human esophageal cancer cell lines KYSE30 and KYSE150...
October 2016: Cancer Science
https://www.readbyqxmd.com/read/27422517/leucine-metabolism-in-t-cell-activation-mtor-signaling-and-beyond
#20
REVIEW
Elitsa A Ananieva, Jonathan D Powell, Susan M Hutson
In connection with the increasing interest in metabolic regulation of the immune response, this review discusses current advances in understanding the role of leucine and leucine metabolism in T lymphocyte (T cell) activation. T cell activation during the development of an immune response depends on metabolic reprogramming to ensure that sufficient nutrients and energy are taken up by the highly proliferating T cells. Leucine has been described as an important essential amino acid and a nutrient signal that activates complex 1 of the mammalian target of rapamycin (mTORC1), which is a critical regulator of T cell proliferation, differentiation, and function...
July 2016: Advances in Nutrition
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