Fig. 5
From: Cancer cachexia: molecular basis and therapeutic advances
Metabolic remodeling in cancer cachexia and its regulatory effects on cellular functions. a The network diagram above illustrates the profound metabolic dysregulation associated with cancer cachexia, such as decreased hepatic ketogenesis, impaired lactate metabolism, elevated hepatic triglyceride accumulation, reduced gut microbiota-derived SCFA production, and suppressed protein synthesis. In glucose metabolism and the TCA cycle, an increase in energy consumption accompanied by an abnormal shift toward anaerobic glycolysis exacerbates the imbalance between energy supply and demand. In fat metabolism, accelerated fat breakdown coexists with WAT browning, resulting in rapid depletion of body fat reserves. In protein metabolism, intensified protein degradation coupled with weakened synthetic capacity leads to significant muscle wasting. b The effects of metabolites on immune and stromal cells include phagocytosis and polarization of macrophages, proliferation and effector functions of T cells, ECM production by fibroblasts, and angiogenesis in endothelial cells. The arrow line represents activation, and the blunt-headed arrow represents inhibition. Abbreviations: BAs bile acid, CoA coenzyme A, 3PG 3-phosphoglycerate, GLUT glucose transporter type, GSSG oxidized glutathione, KB ketone body, Pyr pyruvate, α-KG α-ketoglutarate, MPC mitochondrial pyruvate carrier, APP acute phase protein, FAs fatty acids, VLDL very low-density lipoprotein, TSC22D4 transforming growth factor β1-stimulated clone 22D4, Arg arginine, Leu leucine, Met methionine, Ser serine, Gly glycine, Cys cysteine, Glu glutamate, SAM S-adenosylmethionine, TCF7 transcription factor 7, MMP9 matrix metalloproteinases-9, IFP interstitial fluid pressure. This figure was created with BioRender (https://biorender.com)
