重磅突破！能量通量理论首次揭开危重患者肥胖之谜，医学界沸腾

Core Viewpoint - The article discusses the metabolic reprogramming in critically ill patients, emphasizing the importance of understanding energy flow and immune response mechanisms to improve treatment outcomes [6][9][27]. Metabolic Regulation Principles - The priority of substrate utilization in normal conditions is glucose and glycogen first, followed by fats and proteins. In critical illness, metabolism prioritizes the needs of immune and inflammatory cells, leading to significant breakdown of muscle and fat tissues to support immune cell synthesis [10][11]. - The liver and kidneys significantly enhance gluconeogenesis during critical illness, utilizing lactate, glycerol, and amino acids as substrates, with the Cori cycle playing a key role in glucose regeneration [13]. Immune and Inflammatory Cell Metabolic Reprogramming - Immune cells, such as M1 macrophages and activated T cells, primarily rely on aerobic glycolysis (Warburg effect) for rapid ATP production and biosynthetic precursors, which supports inflammatory responses but has a lower energy yield compared to mitochondrial metabolism [16][18]. - Metabolites like succinate and itaconate can regulate gene expression through epigenetic modifications, influencing inflammation and immune responses [17]. Changes in Adipose Tissue and Skeletal Muscle - In critical illness, white adipose tissue may convert to brown adipose tissue, enhancing thermogenic capacity. The "obesity paradox" suggests that obese individuals may have better survival rates in critical conditions due to greater energy reserves and anti-inflammatory factors [20]. - Muscle protein breakdown is significantly increased due to enhanced ubiquitin-proteasome and autophagy mechanisms, leading to muscle wasting and potential long-term functional impairments post-recovery [22][26]. Conclusion - The body adapts through metabolic reprogramming during critical illness to enhance immune defense and survival, with a focus on the roles of immune cell metabolism and the breakdown of skeletal muscle and adipose tissue. Future research should explore innovative interventions targeting metabolic pathways to improve clinical outcomes for critically ill patients [27].