Fig. 1

Increased lipolytic activities in white adipocytes and thermogenesis in beige and brown adipocytes contribute to excessive fat expenditure in cachexia. In cachexia, increased catecholamines, corticosteroids and inflammatory cytokines promote lipid lipolysis via active PKA/PKG signaling, causing the hydrolysis of lipid droplets as mediated by ATGL/HSL/Peprelin in white adipocytes. In addition, activated PKA/PKG signaling promotes the transcriptional regulation of white adipose tissue browning as characterized by the upregulated expression of Ucp-1, Pparγ and Pdrm16. This process produces large amounts of FFAs, which contribute to mitochondrial thermogenesis in brown and beige adipocytes, accelerating adipose expenditure. Additionally, excessive FFAs efflux into peripheral tissue or organs leads to ectopic fat deposition, such as that observed in atherosclerosis and hepatic steatosis, causing insulin resistance. PKA/PKG protein kinase A/G; ATGL lipases adipose triglyceride lipase; HSL hormone‐sensitive lipase; Ucp-1 uncoupling protein 1; Pparγ peroxisome proliferator-activated receptor gamma; Pdrm16 PR domain-containing 16; FFAs free fatty acids