Bajgar Adam, Krejčová Gabriela, Doležal Tomáš
Department of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czechia.
Front Cell Dev Biol. 2021 Feb 15;9:629238. doi: 10.3389/fcell.2021.629238. eCollection 2021.
Insulin resistance and cachexia represent severe metabolic syndromes accompanying a variety of human pathological states, from life-threatening cancer and sepsis to chronic inflammatory states, such as obesity and autoimmune disorders. Although the origin of these metabolic syndromes has not been fully comprehended yet, a growing body of evidence indicates their possible interconnection with the acute and chronic activation of an innate immune response. Current progress in insect immuno-metabolic research reveals that the induction of insulin resistance might represent an adaptive mechanism during the acute phase of bacterial infection. In , insulin resistance is induced by signaling factors released by bactericidal macrophages as a reflection of their metabolic polarization toward aerobic glycolysis. Such metabolic adaptation enables them to combat the invading pathogens efficiently but also makes them highly nutritionally demanding. Therefore, systemic metabolism has to be adjusted upon macrophage activation to provide them with nutrients and thus support the immune function. That anticipates the involvement of macrophage-derived systemic factors mediating the inter-organ signaling between macrophages and central energy-storing organs. Although it is crucial to coordinate the macrophage cellular metabolism with systemic metabolic changes during the acute phase of bacterial infection, the action of macrophage-derived factors may become maladaptive if chronic or in case of infection by an intracellular pathogen. We hypothesize that insulin resistance evoked by macrophage-derived signaling factors represents an adaptive mechanism for the mobilization of sources and their preferential delivery toward the activated immune system. We consider here the validity of the presented model for mammals and human medicine. The adoption of aerobic glycolysis by bactericidal macrophages as well as the induction of insulin resistance by macrophage-derived factors are conserved between insects and mammals. Chronic insulin resistance is at the base of many human metabolically conditioned diseases such as non-alcoholic steatohepatitis, atherosclerosis, diabetes, and cachexia. Therefore, revealing the original biological relevance of cytokine-induced insulin resistance may help to develop a suitable strategy for treating these frequent diseases.
胰岛素抵抗和恶病质是伴随多种人类病理状态的严重代谢综合征，从危及生命的癌症和脓毒症到慢性炎症状态，如肥胖症和自身免疫性疾病。尽管这些代谢综合征的起源尚未完全明了，但越来越多的证据表明它们可能与先天性免疫反应的急性和慢性激活相互关联。昆虫免疫代谢研究的当前进展表明，胰岛素抵抗的诱导可能是细菌感染急性期的一种适应性机制。在细菌感染过程中，胰岛素抵抗是由杀菌性巨噬细胞释放的信号因子诱导产生的，这反映了它们向有氧糖酵解的代谢极化。这种代谢适应使它们能够有效地对抗入侵的病原体，但也使它们对营养的需求极高。因此，巨噬细胞激活后，全身代谢必须进行调整，为它们提供营养，从而支持免疫功能。这预示着巨噬细胞衍生的全身因子参与介导巨噬细胞与中央能量储存器官之间的器官间信号传递。尽管在细菌感染急性期协调巨噬细胞的细胞代谢与全身代谢变化至关重要，但如果是慢性感染或细胞内病原体感染，巨噬细胞衍生因子的作用可能会变得适应不良。我们假设，巨噬细胞衍生的信号因子引起的胰岛素抵抗是一种动员资源并将其优先输送到激活的免疫系统的适应性机制。我们在此考虑所提出的模型对哺乳动物和人类医学的有效性。杀菌性巨噬细胞采用有氧糖酵解以及巨噬细胞衍生因子诱导胰岛素抵抗在昆虫和哺乳动物之间是保守的。慢性胰岛素抵抗是许多人类代谢性疾病的基础，如非酒精性脂肪性肝炎、动脉粥样硬化、糖尿病和恶病质。因此，揭示细胞因子诱导的胰岛素抵抗的原始生物学相关性可能有助于制定治疗这些常见疾病的合适策略。
