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Abstract: Zinc-α2-glycoprotein (ZAG), a lipid mobilizing factor, is expressed in mouse adipose tissue and is markedly upregulated in mice with cancer cachexia. We have explored whether ZAG is expressed and secreted by human adipocytes, using SGBS cells, and examined the regulation of ZAG expression. ZAG mRNA was detected by RT-PCR in mature human adipocytes and in SGBS cells post-, but not pre-, differentiation to adipocytes. Relative ZAG mRNA levels increased rapidly after differentiation of SGBS cells, peaking at day 8 post-induction. ZAG protein was evident in differentiated adipocytes (by day 3) and also detected in the culture medium (by day 6) post-induction. The PPARγ agonist rosiglitazone induced a 3-fold increase in ZAG mRNA level, while TNF-α led to a 4-fold decrease. Human adipocytes express and secrete ZAG, with ZAG expression being regulated particularly through TNF-α and the PPARγ nuclear receptor. ZAG is a novel adipokine, which may be involved in the local regulation of adipose tissue function. [Copyright &y& Elsevier]

A great deal of attention has focused on the central role of alpha melanocyte-stimulating hormone (α-MSH) and its antagonism at the melanocortin-4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and α-MSH in humans. We aimed to determine whether circulating α-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions. Circulating α-MSH, AgRP and leptin were measured in both lean ( n = 11) and obese ( n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4–6 days) for rapid weight loss or a very low calorie diet (VLCD, 2·6 MJ/day) (11–12 days) for less rapid weight loss, in both the lean and obese volunteers. At baseline, prior to any weight loss both plasma α-MSH (15·8 ± 1·2 vs. 5·8 ± 1·0 pmol/l ± SEM; P < 0·001) and AgRP (49·4 ± 2·4 vs. 10·1 ± 0·9 pg/ml ± SEM; P < 0·001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass ( P < 0·001), percentage body fat ( P < 0·001) and leptin ( P < 0·05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11·1 ± 1·6 vs. 21·6 ± 3·1 pg/ml ± SEM; P < 0·05) but not in the VLCD subjects or in the obese, while α-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers. We show a difference in α-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects. [ABSTRACT FROM AUTHOR]