Lipid mobilization in cachexia: mechanisms and mediators

Curr Opin Support Palliat Care. 2011 Dec;5(4):356-60. doi: 10.1097/SPC.0b013e32834bde0e.

Abstract

Purpose of review: Extensive loss of body fat is considered as a hallmark of cancer cachexia which affects the quality of life and shortens survival. Evidence suggests that increased lipid mobilization has a central role in adipose tissue wasting. This review summarizes recent progress, with a particular focus on the mechanisms and the potential mediators of lipid mobilization in cachexia.

Recent findings: Accelerated fat loss begins at around 7 months before death and predicts survival in advance cancer patients. Adipose tissue remodelling with reduced lipid storage is evident in cancer patients with cachexia. Enhanced lipolysis regulated by adipose triglyceride lipase and hormone-sensitive lipase could be essential for triacylglycerol degradation. In addition to cytokines, other factors such as zinc-α2-glycoprotein (ZAG) are implicated in adipose atrophy. ZAG expression and release by adipose tissue is upregulated in weight-losing cancer patients, and serum ZAG has been shown as a marker for pancreatic cancer-associated cachexia, suggesting that ZAG may function locally and systemically to stimulate lipid mobilization.

Summary: Recent progress in clinical and mechanistic studies provides some new insights into the pathogenesis of adipose atrophy in cachexia. Further studies to unravel the mechanisms and mediators may lead to novel pharmacological targets to ameliorate cachexia syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adiposity*
  • Biomarkers
  • Cachexia / etiology*
  • Cachexia / metabolism
  • Cytokines / metabolism
  • Humans
  • Inflammation Mediators / metabolism*
  • Lipid Metabolism*
  • Lipolysis*
  • Neoplasms / complications*
  • Neoplasms / metabolism
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Interacting Protein 1
  • Risk Factors
  • Seminal Plasma Proteins / metabolism
  • Time Factors
  • Zn-Alpha-2-Glycoprotein

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Nuclear Proteins
  • Nuclear Receptor Interacting Protein 1
  • Seminal Plasma Proteins
  • Zn-Alpha-2-Glycoprotein