Selenium-dependent metabolic reprogramming during inflammation and resolution.

Area of Science:

• Biochemistry
• Immunology
• Metabolomics

Background:

• Selenium (Se) is crucial for selenoproteins, which regulate redox homeostasis and immune responses.
• The metabolic reprogramming underlying inflammation resolution is not fully understood.

Purpose of the Study:

• To investigate the role of selenium in metabolic reprogramming during inflammation and resolution.
• To elucidate the mechanistic link between selenium, macrophage metabolism, and the resolution of inflammation.

Main Methods:

• Murine bone marrow-derived macrophages were stimulated with lipopolysaccharide (LPS) in the presence or absence of selenium.
• Proteomics, metabolomics, and machine learning were used to analyze temporal changes.
• Macrophage function was assessed in selenium-deficient cells and using enzyme inhibitors in vivo.

Main Results:

• Selenium supplementation reprogrammed cellular metabolism upon LPS stimulation, enhancing the pentose phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation.
• Metabolic adaptation toward proresolving phenotypes was observed, particularly involving succinate dehydrogenase complex, pyruvate kinase, and sedoheptulokinase.
• Selenium-dependent metabolic modulation promoted a phenotypic transition toward alternatively activated macrophages, facilitating inflammation resolution.
• Inhibition of succinate dehydrogenase complex impaired selenium's proresolving effects in vivo.

Conclusions:

• Cellular selenium plays a critical role in facilitating anti-inflammation and proresolution through metabolic reprogramming.
• Selenium enhances macrophage oxidative phosphorylation, crucial for regulating inflammation and its timely resolution.
• Targeting selenium-dependent metabolic pathways offers a novel strategy for managing inflammatory conditions.