Catabolism of adipose tissue by a tumour-produced lipid-mobilising factor

Int J Cancer. 1999 Jan 29;80(3):444-7. doi: 10.1002/(sici)1097-0215(19990129)80:3<444::aid-ijc18>3.0.co;2-u.

Abstract

Induction of lipolysis in murine white adipocytes by a tumour lipid-mobilising factor (LMF) was associated with stimulation of adenylate cyclase in adipocyte plasma membrane preparations. Induction of lipolysis was attenuated by the adenylate cyclase inhibitor MDL12330A and the protein kinase A inhibitor H8, suggesting that cAMP was the intracellular mediator of induction. The effect of LMF on adenylate cyclase was responsive to GTP, with low concentrations (0.1 microM) causing stimulation and high concentrations (10 microM) causing inhibition, suggesting the involvement of both stimulatory (Gs) and inhibitory (Gi) guanine nucleotide-binding proteins. At a concentration of 10 microM, propranolol noncompetitively reduced the induction of lipolysis by LMF. Thus, lipolysis in white adipose tissue during the process of cancer cachexia is mediated by a tumour factor which stimulates cAMP production, possibly through a beta-adrenergic receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Induction
  • Enzyme Inhibitors / pharmacology
  • Female
  • Imines / pharmacology
  • Lipid Mobilization
  • Lipolysis* / drug effects
  • Male
  • Membrane Lipids / metabolism
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Proteins / pharmacology*
  • Peptides / pharmacology*
  • Propranolol / pharmacology

Substances

  • Adenylyl Cyclase Inhibitors
  • Enzyme Inhibitors
  • Imines
  • Membrane Lipids
  • Neoplasm Proteins
  • Peptides
  • lipid mobilizing substance
  • RMI 12330A
  • Propranolol
  • Adenylyl Cyclases