Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

Abstract

Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

Immunometabolism and Exercise: New avenues

“…Desta forma, tanto a glicose, que é convertida em lactato, como a glutamina, que é convertida em glutamato, aspartato e lactato, são os principais substratos dessa célula, embora corpos cetônicos e ácidos graxos também sejam utilizados em menor escala, especialmente em condição homeostática (Ardawi & Newsholme, 1984;Yaqoob, Newsholme, & Calder, 1994). Vale destacar alguns hormônios, como a insulina e hormônios da tireoide, que auxiliam na função dos linfócitos, estimulando a glicólise aeróbica, o consumo de glutamina e estimulação do metabolismo aeróbio (Wasinki et al, 2014).…”

“…Os primeiros macrófagos a se acumularem no início da inflamação são caracterizados como M1; quando passam a atuar no processo de recuperação tecidual, mediado por citocinas como IL-10 e fatores de crescimento tumorais (TGFβ1), aumentando a proliferação de mioblastos e crescimento miofibrilar, são polarizados em macrófagos de caráter anti-inflamatório (M2) (Deng, Wehling-Henricks, Villalta, Wang & Tidball, 2012 (Wasinki et al, 2014).…”

When Is It Appropriate to Use Glutamine in Critical Illness?

“…2 Glutamine combined with glucose serves as the most quantitatively important oxidative fuel source for activated immune cells such as lymphocytes. 5,6 Work using lymphocyte cultures has revealed that the proliferative response as well as the differentiation of these cells is dependent on glutamine. 7 In fact, proliferating lymphocytes may have 10-fold greater glutamine utilization compared with resting cells.…”

Effect of Exercise Induced Glutamine on Immune Function.

“…One important mechanism for such changes is alterations in immune functions. Moderate exercise may have predominance over immunity via anti-inflammatory and immunomodulatory effects (Wasinski et al 2014), whereas high intensity exercise raises the concentration of anti-inflammatory cytokines, leading to cause infection by intracellular microorganisms as well as alterations in endocrine system and metabolic regulation (Mondal and Chatterjee 2018). Exercise modulates immune function in a variety of ways through complex interaction of hormones, cytokines, and metabolic changes.…”

“…(Curi et al 1999;Frederick et al 2014).In different functional states, lymphocytes reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production(Frederick et al 2014). Therefore the inability of cell metabolism to congregate the energetic and biosynthetic demands of lymphocytes may upset immune functionality (Caro-Maldonado et al 2012;Wasinski et al 2014). Mononuclear cells have a high-intracellular activity of glutaminase but they cannot synthesize glutamine due to lack of glutamine synthase.…”