Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat.
OBJECTIVE
To investigate the anti-obesity effect of the adipokine zinc-α(2)-glycoprotein (ZAG) in rats and the mechanism of this effect.


METHODS
Mature male Wistar rats (540 ± 83 g) were administered human recombinant ZAG (50 μg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS).


RESULTS
Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect.


CONCLUSIONS
These results show that ZAG produces increased lipid mobilization and utilization in the rat.
Russell
S T
ST
Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, UK.
Tisdale
M J
MJ
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000187:drug effects* / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D029589:Seminal Plasma Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D013851:Thinness / Q000209:etiology; D015431:Weight Loss / Q000502:physiology; D000090203:Zn-Alpha-2-Glycoprotein
D019440:Anti-Obesity Agents; D002352:Carrier Proteins; D051275:Glucose Transporter Type 4; D011994:Recombinant Proteins; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein