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 regula...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.展开更多
A recent study by McDonald et al.(2021)focused on how peripheral glucose metabolism and handling are compromised in amyotrophic lateral sclerosis(ALS).Dysfunctions in glucose and energy metabolism have been identified...A recent study by McDonald et al.(2021)focused on how peripheral glucose metabolism and handling are compromised in amyotrophic lateral sclerosis(ALS).Dysfunctions in glucose and energy metabolism have been identified in transgenic mouse models and patients with ALS.However,how these processes are altered and contribute to disease progression are not fully understood.The aforementioned study has identified several changes to glucose homeostasis in the transgenic SOD1G93A mouse model of ALS at the later stages of the disease.Specifically,the authors found that despite insulin resistance being present,there was increased glucose uptake in ALS mice,and increased glycogen accumulation in the liver.Additionally,there was evidence of glucagon resistance developing in these mice,which supports clinical observations.This perspective outlines the key aspects of glucose metabolism and demonstrates how multiple pathways relating to these processes are compromised in ALS.展开更多
基金support from Motor Neuron Disease Research Institute of Australia(Grant Award Number:GIA1930 and PDF1604)。
文摘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.
基金support from Motor Neuron Disease Research Australia(Grant Award Number:IG1930).
文摘A recent study by McDonald et al.(2021)focused on how peripheral glucose metabolism and handling are compromised in amyotrophic lateral sclerosis(ALS).Dysfunctions in glucose and energy metabolism have been identified in transgenic mouse models and patients with ALS.However,how these processes are altered and contribute to disease progression are not fully understood.The aforementioned study has identified several changes to glucose homeostasis in the transgenic SOD1G93A mouse model of ALS at the later stages of the disease.Specifically,the authors found that despite insulin resistance being present,there was increased glucose uptake in ALS mice,and increased glycogen accumulation in the liver.Additionally,there was evidence of glucagon resistance developing in these mice,which supports clinical observations.This perspective outlines the key aspects of glucose metabolism and demonstrates how multiple pathways relating to these processes are compromised in ALS.
