Effects of dietary glutamine supplementation on immune cell polarization and muscle regeneration in diabetic mice with limb ischemia

Pai, Man Hui; Lei, Cing Syuan; Su, Shiau Tsz; Yeh, Sung Ling; Hou, Yu

doi:10.1007/s00394-019-01951-4

Cited by 10 publications

(10 citation statements)

References 60 publications

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“…Gln elicits many beneficial effects in the setting of ischemia-reperfusion. It reduces oxidative and nitrosative stress and minimizes inflammation by blocking inflammatory mediator release, adhesion molecule expression, the recruitment and infiltration of immune cells into the organ and increases the percentage of alternatively activated macrophages (M2) that support the resolution of inflammation [86,87,89,91]. In addition, Gln inhibits lipid peroxidation, necrosis, and apoptosis following ischemia-reperfusion [85,88,92,93].…”

Section: L-glutamine and Other Cardiovascular Disordersmentioning

confidence: 99%

The Emerging Role of l-Glutamine in Cardiovascular Health and Disease

Durante

2019

Nutrients

112

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Emerging evidence indicates that l-glutamine (Gln) plays a fundamental role in cardiovascular physiology and pathology. By serving as a substrate for the synthesis of DNA, ATP, proteins, and lipids, Gln drives critical processes in vascular cells, including proliferation, migration, apoptosis, senescence, and extracellular matrix deposition. Furthermore, Gln exerts potent antioxidant and anti-inflammatory effects in the circulation by inducing the expression of heme oxygenase-1, heat shock proteins, and glutathione. Gln also promotes cardiovascular health by serving as an l-arginine precursor to optimize nitric oxide synthesis. Importantly, Gln mitigates numerous risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, glucose intolerance, obesity, and diabetes. Many studies demonstrate that Gln supplementation protects against cardiometabolic disease, ischemia-reperfusion injury, sickle cell disease, cardiac injury by inimical stimuli, and may be beneficial in patients with heart failure. However, excessive shunting of Gln to the Krebs cycle can precipitate aberrant angiogenic responses and the development of pulmonary arterial hypertension. In these instances, therapeutic targeting of the enzymes involved in glutaminolysis such as glutaminase-1, Gln synthetase, glutamate dehydrogenase, and amino acid transaminase has shown promise in preclinical models. Future translation studies employing Gln delivery approaches and/or glutaminolysis inhibitors will determine the success of targeting Gln in cardiovascular disease.

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Section: L-glutamine and Other Cardiovascular Disordersmentioning

confidence: 99%

The Emerging Role of l-Glutamine in Cardiovascular Health and Disease

Durante

2019

Nutrients

112

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“…It can be found from the cellular kinetics of repair after skeletal muscle injury that regulatory CD4 + T cells (Treg cells) expressing Foxp3 play a crucial role in the shift in cellular response. Macrophages and conventional T cells not inhibited during the inflammatory phase can bring about many autoimmune myositis such as idiopathic inflammatory myopathy (IIM), and muscular dystrophy can also be caused by excessive production of Tregs cells and prolonged anti-inflammatory and regenerative stages [ 15 ]. Therefore, in order to clarify the role of Tregs cells in the regulatory network of skeletal muscle inflammation, this paper will review recent literature on the relationship of Tregs cells with muscle injury inflammation and repair.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have indicated that the effectiveness of glutamine (GLN) is inhibited after muscle injury, that low levels of GLN stimulates the secretion and oxidation of GLN by infiltrating macrophages, and that GLN released by macrophages can activate mTOR and promote the proliferation and differentiation of MuSCs after the uptake by MuSCs [ 99 ]. Another study has proposed that GLN might up-regulate the number of Treg cells through the IL-2 and IL-2 receptor pathways, and similarly, the administration of GLN can reduce the recruitment of pro-inflammatory macrophages and increase the polarization to anti-inflammatory macrophages [ 15 ]. It can be speculated from the above investigations that there is a negative feedback system in macrophages, and GLN can be an important factor involved in this system.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cells-centered regulatory networks of skeletal muscle inflammation and regeneration

et al. 2022

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As the understanding of skeletal muscle inflammation is increasingly clarified, the role of Treg cells in the treatment of skeletal muscle diseases has attracted more attention in recent years. A consensus has been reached that the regulation of Treg cells is the key to completing the switch of inflammation and repair of skeletal muscle, whose presence directly determine the repairing quality of the injured skeletal muscle. However, the functioning process of Treg cells remains unreported, thereby making it necessary to summarize the current role of Treg cells in skeletal muscle. In this review, the characteristics, origins, and cellular kinetics of these Treg cells are firstly described; Then, the relationship between Treg cells and muscle satellite cells (MuSCs), conventional T cells (Tconv) is discussed (the former is involved in the entire repair and regeneration process, while the latter matters considerably in causing most skeletal muscle autoimmune diseases); Next, focus is placed on the control of Treg cells on the phenotypic switch of macrophages, which is the key to the switch of inflammation; Finally, factors regulating the functional process of Treg cells are analyzed, and a regulatory network centered on Treg cells is summarized. The present study summarizes the cell-mediated interactions in skeletal muscle repair over the past decade, and elucidates the central role of regulatory T cells in this process, so that other researchers can more quickly and comprehensively understand the development and direction of this very field. It is believed that the hereby proposed viewpoints and problems can provide fresh visions for the latecomers.

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“…Consistent with those findings, TNF-α, IL-1β, and IL-6 mRNA expressions in muscles were downregulated. A study performed by our laboratory also revealed that Gln supplementation reduced the muscle M1/M2 ratio and accelerated muscle regeneration in diabetic mice with limb ischemia [ 11 ]. Inflammation is linked to oxidative stress [ 34 ] and tissue hypoxia [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…l -glutamine (Gln) is a pharmaconutrient that has immunomodulatory, anti-inflammatory, and antioxidative properties in critical illnesses [ 8 , 9 ]. A previous study indicated that Gln supplementation inhibits whole-body protein degradation in patients with muscular dystrophy [ 10 ] and attenuates muscular inflammation which contributes to muscle regeneration in diabetic mice subjected to limb ischemia [ 11 ]. Leucine, an essential amino acid, is considered a modulator of skeletal muscle protein metabolism by inhibiting protein breakdown and stimulating protein synthesis [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries

Hou

Pai

et al. 2021

IJMS

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This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

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Effects of dietary glutamine supplementation on immune cell polarization and muscle regeneration in diabetic mice with limb ischemia

Cited by 10 publications

References 60 publications

The Emerging Role of l-Glutamine in Cardiovascular Health and Disease

The Emerging Role of l-Glutamine in Cardiovascular Health and Disease

Regulatory T cells-centered regulatory networks of skeletal muscle inflammation and regeneration

Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries

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