The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting

What is it about?

Different end-stage diseases and various cancers are associated with cachexia, a complex condition of adipose and skeletal muscle tissue wasting. One of the factors that contributes to energy wasting in cachexia is browning of white adipose tissue (WAT), a phenomenon in which pools of brown adipocytes are generated within WAT. Brown adipocytes consume glucose and fatty acids and dissipate energy as heat by uncoupled respiration. Zinc-α2-glycoprotein (ZAG) is a soluble protein and its levels are elevated in the serum of various cancer patients. To understand the consequence of elevated circulating levels of ZAG, we generated and implanted ZAG-overexpressing cells in mice, and investigated its effect on adipose tissue metabolism. In this study, we demonstrated that ZAG induces WAT browning in mice. ZAG activated PPARγ/Ebf2/Prdm16 signaling pathway which determines brown cell fate. Therefore, inhibition of ZAG might be a promising strategy to block WAT browning-associated energy wasting in cachexia.

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