Zinc-alpha2-glycoprotein in cachexia and obesity.
OBJECTIVE
Control of adipose mass is important in the treatment of both cachexia and obesity. This review focuses on a novel adipokine, zinc-alpha2-glycoprotein (ZAG), which plays an important role in the mobilization and utilization of stored lipids.


RESULTS
An increased lipolysis is responsible for the loss of adipose tissue in cachexia, through an increased lipolytic response to catecholamines, arising from an increased expression of hormone-sensitive lipase. In obesity, there is a decreased response of adipocytes to catecholamines and reduced expression of hormone-sensitive lipase. ZAG was identified as a lipolytic factor produced by certain cachexia-inducing tumours, and subsequently adipose tissue (both white and brown), the expression of which was found to increase in cachexia. In contrast, ZAG expression is low in obesity. ZAG not only increases lipolysis in white adipose tissue through the classical cyclic AMP pathway, but also stimulates an increase in expression of uncoupling protein-1 in brown adipose tissue, which would stimulate utilization of the release lipid to generate heat. Homozygous ZAG null mice show an increase in body weight, especially when fed a high-fat diet, whereas adipocytes from such animals show a resistance to lipolysis by catecholamines and agents that increase cyclic AMP levels.


CONCLUSIONS
These results suggest that ZAG may play an important role in the regulation of adipose mass in obesity and cachexia.
Tisdale
Michael J
MJ
Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK. m.j.tisdale@aston.ac.uk
D054392:Adipokines; D000273:Adipose Tissue / Q000502:physiology; D053898:Biosynthetic Pathways / Q000502:physiology; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology*; D002352:Carrier Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D009765:Obesity / Q000150:complications*; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D002352:Carrier Proteins; D006023:Glycoproteins; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein