Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse.
OBJECTIVE
To investigate the mechanism of the lipid depletion by zinc-α(2)-glycoprotein (ZAG).


METHODS
Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts.


RESULTS
Treatment of these animals for 15 days with ZAG (100  μg, intravenously, daily) resulted in a reduction of body weight of 6.55  g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4 °C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway.


CONCLUSIONS
These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli.
Russell
S T
ST
Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, UK.
Tisdale
M J
MJ
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000378:metabolism / Q000494:pharmacology*; D002787:Sterol Esterase / Q000378:metabolism; D000090203:Zn-Alpha-2-Glycoprotein; D000217:Acyltransferases
D019440:Anti-Obesity Agents; D002352:Carrier Proteins; D008049:Lipase; D029589:Seminal Plasma Proteins; D002787:Sterol Esterase; D000090203:Zn-Alpha-2-Glycoprotein; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases