Zinc-alpha2-glycoprotein in cachexia and obesity.

PURPOSE OF REVIEW

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.

RECENT FINDINGS

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.

SUMMARY

These results suggest that ZAG may play an important role in the regulation of adipose mass in obesity and cachexia.