B. Islam-ali et al., Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF), BR J CANC, 85(5), 2001, pp. 758-763
Adipocytes isolated from cachectic mice bearing the MAC 16 tumour showed ov
er a 3-fold increase in lipolytic response to both low concentrations of is
oprenaline and a tumour-derived lipid mobilizing factor (LMF). This was ref
lected by an enhanced stimulation of adenylate cyclase in plasma membrane f
ractions of adipocytes in the presence of both factors. There was no up-reg
ulation of adenylate cyclase in response to forskolin, suggesting that the
effect arose from a change in receptor number or G-protein expression. Immu
noblotting of adipocyte membranes from mice bearing the MAC16 tumour showed
an increased expression of Gas up to 10% weight loss and a reciprocal decr
ease in Ga. There was also an increased expression of Gas and a decrease in
Ga in adipose tissue from a patient with cancer-associated weight loss com
pared with a non-cachectic cancer patient. The changes in G-protein express
ion were also seen in adipose tissue of normal mice administered pure LMF a
s well as in 3T3L1 adipocytes in vitro. The changes in G-protein expression
induced by LMF were attenuated by the polyunsaturated fatty acid, eicosape
ntaenoic acid (EPA), This suggests that this tumour-derived lipolytic facto
r acts to sensitize adipose tissue to lipolytic stimuli, and that this effe
ct is attenuated by EPA, which is known to preserve adipose tissue in cance
r cachexia. (C) 2001 Cancer Research Campaign.