Amino acid supplementation and impact on immune function in the context of exercise

Cruzat, Vinícius Fernandes; Krause, Maurício; Newsholme, Philip

doi:10.1186/s12970-014-0061-8

Cited by 126 publications

(115 citation statements)

References 131 publications

(187 reference statements)

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“…A growing body of evidence demonstrates that metabolic reprogramming of immune cells is extremely important for the development of an adequate immune response [3][4][5]. Immune cells use glutamine at similar or greater rates than glucose during several inflammatory states as sepsis, surgery recovery and high-intensity training [25][26][27]. Herein, we demonstrated an upregulation of the genes associated with glutaminolysis as well as an increase in glutamine consumption of L. donovani-infected macrophages.…”

Section: Discussionmentioning

confidence: 66%

Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis

et al. 2020

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BackgroundThe disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown.Visceral leishmaniasis is a life threatening neglected tropical disease affecting around 500,000 and killing 50,000 individuals a year. Despite its obligatory dependence on host cell metabolism and the lack of effective, non-toxic, orally bioavailable anti-leishmanial drugs, Leishmania-perturbed host cell metabolomes and its relation to anti-leishmanial chemotherapy remains unexplored. Transcriptomic analysis performed on L. donovaniinfected macrophages identified patterns of gene expression associated with glutamine metabolism. In vitro and in vivo pharmacological inhibition of glutaminase (GLS), which catalyzes the first reaction in the primary pathway for the catabolism of glutamine, significantly increased the susceptibility to infection demonstrating the role of glutamine metabolism to L. donovani infection. More importantly, we demonstrated that glutamine supplementation during miltefosine treatment potentiates L. donovani clearance through the development of a more effective anti-Leishmania innate and adaptive immune response. Overall, our work demonstrated that glutamine-miltefosine synergy is a novel combined host-and pathogen-directed treatment for combating visceral leishmaniasis.

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Section: Discussionmentioning

confidence: 66%

Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis

et al. 2020

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“…First, we performed a BCAA concentration-response curve to evaluate the phosphorylation of both pathways, using a concentration range from 0. found in some individuals if consumed daily 6-20 g BCAA for 2 months in 2 or 3 cycles per year or for uninterrupted period of time. 5,6 As shown in Figure 1A PI3K/Akt pathway is as an upstream activator of mTORC1 in different cell types. 22,27,28 In ECs, BCAA promoted Akt phosphorylation ( Figure 1D).…”

Section: Fluorimetric Peroxynitrite Assaymentioning

confidence: 99%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

103

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Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA‐induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.

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“…The amino acids in the placenta are so called phytohormones and have multiple functions, such as antioxidant, fuel provision, energy homeostasis, immune responses, recovery, development and growth. 13 Arginine, lysine, and carnitine are very effective on menopausal symptoms such as hot flushes, osteoporosis, and weight loss. 14,15 However, proline which is a major amino acid found in the placenta remains poorly defined as potential therapeutic agents for relief postmenopausal symptoms.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of proline in the treatment of menopause

Nam

Yoou

Kim

et al. 2016

Exp Biol Med (Maywood)

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The amino acids in the placenta have multiple functions; however, the therapeutic effects of proline remain poorly for relief postmenopausal symptoms. The aim of present study was to evaluate the effects of proline in the treatment of menopause using in vitro and in vivo models. We assessed the therapeutic effects and regulatory mechanisms of proline by using MCF-7 estrogen-dependent cells, MG63 osteoblast cells, and ovariectomized mice model. An in vivo study was carried out in eight-weekold sham and ovariectomized group. The ovariectomized mouse was further subdivided into two groups administered orally with 17b-estradiol or proline (10 mg/kg/day) for eight weeks. Proline significantly increased cell proliferation and Ki-67 levels in MCF-7 cells and enhanced cell proliferation, alkaline phosphatase activity, extracellular signal-regulated kinase phosphorylation, and glutamyl-prolyl-tRNA synthetase activation in MG63 cells. The estrogen receptor-b and estrogen-response elements luciferase activity were significantly increased by proline in MCF-7 and MG63 cells. In ovariectomized mice, oral administration of proline (10 mg/kg/day) for eight weeks significantly reduced body and vaginal weights. Proline also significantly increased serum estradiol and alkaline phosphatase levels, whereas serum luteinizing hormone was decreased by proline. In addition, detailed microcomputed tomography analysis showed that the proline notably enhanced bone mineral density, trabecular bone volume, and trabecular number in ovariectomized mice. Those findings implied that proline can be a promising candidate for the treatment of menopause.

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Amino acid supplementation and impact on immune function in the context of exercise

Cited by 126 publications

References 131 publications

Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis

Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Efficacy of proline in the treatment of menopause

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