Purpose of review: Cachexia development is a feature of cancer as well as other chronic diseases. Fat mass loss appears of greatest importance in cachexia, as it is related to poorer survival. Zinc-α2-glycoprotein (ZAG), firstly isolated in human plasma 50 years ago, has emerged as a novel adipokine, which plays an important role in mobilization and utilization of lipids. This review will focus on recent evidences of ZAG as a fat catabolic marker in cancer and other diseases complicated by cachexia.
Recent findings: ZAG is a lipolytic factor produced by certain cachexia-inducing tumuors and by adipose tissue. It increases lipolysis in white adipose tissue through cyclic-AMP pathway and stimulates uncoupling protein-1 in brown adipose tissue leading to heat generation. In cancer cachexia, ZAG release from white adipocytes is elevated and closely related to body weight loss. In cardiac cachexia, ZAG and circulating free fatty acids are closely related, suggesting a causative role in fat catabolism.
Summary: ZAG may play an important role, probably as an autocrine/paracrine modulator of adipose mass in cachexia. A better comprehension of ZAG involvement in fat wasting mechanisms will be useful in the development of new therapeutic agents.