Complement:a global immunometabolic regulator in amyotrophic lateral sclerosis

Recently,McDonald et al.(2020)proposed that complement causes a metabolic switch to lipid consumption in amyotrophic lateral sclerosis(ALS),which raises the possibility of complement as a global immunometabolic regulator.In ALS,neuromuscular degeneration occurs concurrently with complement-mediated inflammation,glucose intolerance,and elevated lipid consumption.Moreover,complement is being increasingly recognized as a metabolic regulator that can induce insulin resistance and alter fuel source selection.Thus,the authors propose that chronic complement activation may be driving metabolic reprogramming in ALS,which has broad implications for the field of immunometabolism and would be the first mechanistic explanation of the“lipid switch”in ALS.Specifically,it suggests that complement can drive a global shift in resources during inflammation,in which glucose is redirected from peripheral tissues to immune cells to support their inflammatory actions.