Adipose zinc-α2-glycoprotein is a catabolic marker in cancer and noncancerous states


Mikael Rydén, MD, PhD, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.
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Abstract.  Rydén M, Agustsson T, Andersson J, Bolinder J, Toft E, Arner P (Intervention and Technology (CLINTEC), Karolinska University Hospital, Huddinge, Stockholm, Sweden; Norrlands University Hospital, Umeå, Sweden; and Ersta Hospital, Stockholm, Sweden). Adipose zinc-α2-glycoprotein is a catabolic marker in cancer and noncancerous states. J Intern Med 2012; 271: 414–420

Objective.  Zinc-α2-glycoprotein (ZAG) has been proposed as a tumour-derived cancer cachexia factor. However, ZAG is produced by some normal tissues, including white adipose tissue (WAT), and high serum ZAG levels are present in nonmalignant conditions. We determined whether human WAT contributes to serum ZAG levels and how serum and WAT-secreted ZAG levels correlate with catabolism in patients with cancer and in obese subjects undergoing a very low-calorie diet (VLCD) for 11 days.

Design/subjects.  ZAG levels in serum and in conditioned medium from WAT/adipocytes were determined by enzyme-linked immunosorbent assay. ZAG release from WAT in vivo was determined in 10 healthy subjects. The correlation between ZAG and cachexia was studied in 34 patients with newly diagnosed gastrointestinal cancer. The impact of a VLCD on ZAG release and serum levels was assessed in 10 obese women.

Results.  ZAG was released from abdominal WAT and adipocytes in vitro. However, the arteriovenous differences in vivo showed that there was no significant contribution of WAT to the circulating levels. WAT-secreted but not serum ZAG correlated positively with poor nutritional status but not with fat mass (or body mass index) in patients with gastrointestinal cancer. In obese subjects on a VLCD, ZAG secretion from WAT increased significantly whereas serum levels remained unaltered.

Conclusions.  ZAG is released from human WAT, but this tissue does not contribute significantly to the circulating levels. WAT-secreted ZAG correlates with nutritional status but not with fat mass in both cancer and nonmalignant conditions. Adipose ZAG is therefore a local factor activated primarily by the catabolic state per se.