The mode of action of a lipid mobilising factor in cancer cachexia

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Cachexia is characterised by a progressive weight loss due to depletion of both skeletal muscle and adipose tissue. The loss of adipose tissue is due to the production of a tumour-derived lipid mobilising factor (LMF), which has been shown to directly induce lipolysis in isolated epididymal murine white adipocytes. The administration of LMF to a non-tumour bearing mice produced a rapid weight loss, with a specific reduction in carcass lipid with also some redistribution of lipid with the accumulation of lipid in the liver. There was also up-regulation of uncoupling protein-1 and -2 mRNA and protein expression in brown adipose tissue, suggesting that an adaptive process occurs due to increased energy mobilisation. There was also up-regulation of UCP-2 in the livers of LMF treated mice, suggesting a protective mechanism to the build up of lipid in the livers, which would produce free radical by-products. LMF was also shown to stimulate cyclic AMP production in CHO-K1 cells transfected with human -3 adrenergic receptors and inhibited by the -β3 antagonist SR59230A. LMF binding was also inhibited by SR59230A in isolated receptors. This suggests that LMF mediates its effects through a β3 adrenergic receptor. There were also changes in glucose and fatty acid uptake in LMF treated mice, which suggests metabolic changes are occurring. The study suggests that a tumour derived lipolytic factor acts through the 3 adrenoceptor producing effects on lipid mobilisation, energy expenditure and glucose metabolism.
Date of AwardApr 2002
LanguageEnglish
SupervisorMichael J Tisdale (Supervisor)

Keywords

  • lipid mobilising factor
  • lipolysis
  • uncoupling proteins
  • β3 adrenergic
  • receptors
  • zinc-α2-glycoprotein
  • glucose uptake

Cite this

The mode of action of a lipid mobilising factor in cancer cachexia
Russell, S. T. (Author). Apr 2002

Student thesis: Doctoral ThesisDoctor of Philosophy