cachexia

see also:

• neoplasia / cancer / tumours
• oncology

• “Most people with cancer die of cachexia instead of cancer”

• blocking IL-6 from binding to neurons in a part of the brain called the area postrema (AP) prevents cachexia in mice, this worked by either:¹⁾
  • neutralized IL-6 with custom antibodies
  • using CRISPR to reduce the levels of IL-6 receptors in AP neurons
• see also: interleukin-6 (IL-6)

• growth differentiation factor 15 (GDF15) is a stress hormone which can trigger nausea by binding to GFRAL receptors in the brainstem and is a potent anorectic factor
• sensitivity to GDF15 is the cause of hyperemesis gravidarum and serum levels can also be 10-100x higher than normal in patients with advanced cancers

• cancer-induced systemic inflammation disrupts vagal tone via increased CCL2/CCR chemokine acting in the CNS
• this dysregulation leads to reduced acetylcholine release from vagal synapses and resulting depletion of hepatic HNF4α, a crucial transcription factor governing liver protein metabolism
• the resulting hepatic dysfunction amplifies systemic inflammation, driving the cachectic symptoms that afflict many cancer patients
• restoring vagal function by targeting the right cervical vagus nerve reestablished normal liver metabolism, reduced systemic inflammation, and alleviated cachexia's clinical manifestations ²⁾