Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients.
BACKGROUND
Profound loss of adipose tissue is a hallmark of cancer cachexia. Zinc-α2-glycoprotein (ZAG), a recently identified adipokine, is suggested as a candidate in lipid catabolism.


METHODS
In the first study, eight weight-stable and 17 cachectic cancer patients (weight loss 5% in previous 6 months) were recruited. Zinc-α2-glycoprotein mRNA and protein expression were assessed in subcutaneous adipose tissue (SAT), subcutaneous adipose tissue morphology was examined and serum ZAG concentrations were quantified. In the second cohort, ZAG release by SAT was determined in 18 weight-stable and 15 cachectic cancer patients. The effect of ZAG on lipolysis was evaluated in vitro.


RESULTS
Subcutaneous adipose tissue remodelling in cancer cachexia was evident through shrunken adipocytes with increased fibrosis. In cachectic cancer patients, ZAG mRNA was upregulated (2.7-fold, P=0.028) while leptin mRNA decreased (2.2-fold, P=0.018); serum ZAG levels were found to be unaffected. Zinc-α2-glycoprotein mRNA correlated positively with weight loss (r=0.51, P=0.01) and serum glycerol levels (r=0.57, P=0.003). Zinc-α2-glycoprotein release by SAT was also elevated in cachectic patients (1.5-fold, P=0.024) and correlated with weight loss (r=0.50, P=0.003). Recombinant ZAG stimulated lipolysis in human adipocytes.


CONCLUSIONS
Zinc-α2-glycoprotein expression and secretion by adipose tissue is enhanced in cachectic cancer patients. Given its lipid-mobilising effect, ZAG may contribute to adipose atrophy associated with cancer cachexia in human beings.
Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
T
T
Mracek
N A
NA
Stephens
D
D
Gao
Y
Y
Bao
J A
JA
Ross
M
M
Rydén
P
P
Arner
P
P
Trayhurn
K C H
KC
Fearon
C
C
Bing
D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000096:biosynthesis; D000368:Aged; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D008660:Metabolism; D008875:Middle Aged; D029589:Seminal Plasma Proteins / Q000096:biosynthesis*; D050151:Subcutaneous Fat / Q000378:metabolism*; D015431:Weight Loss; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein
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