Probing the Biology of Zinc Alpha2-Glycoprotein and the role it plays in cachexia

Cachexia is a metabolic disease that results in drastic weight loss and muscle wasting. 20% of total cancer patients will die due to cachexia related complications. ZAG contributes to the regulation of weight and body fat through lipid and glucose metabolism. In healthy individuals, ZAG exerts a homeostasis effect by inducing lipolysis of adipose tissue to help reduce fat storage and overall weight. ZAG is upregulated in various carcinomas and cancer patients with upregulated ZAG are observed to lose weight rapidly. The mutants of ZAG which are the 4 amino acids Tryptophan 148, Arginine 73, Phenylalanine 101, Isoleucine 76 have all been mutated to Alanine. The effect of mutants and the wild type ZAG can also be found out by conducting experiments. ZAG has a potential lipid binding site that could be imperative to the function of ZAG. A lipolysis colorimetric kit allows us to measure the ZAG variants effects on 3T3 adipose cells to determine what β-adrenoreceptor signaling pathways are being utilized in its lipolytic effect. The Tryptophan-Alanine mutant showed increased lipolysis after 1h treatment than other variants. The time period is also a rate limiting step which can play major factor in lipolysis. The ultimate goal is to identify the ligand(s) and the interactions between them and ZAG. The design of a therapeutic would give patients options of treatments brought about by attenuating the weight loss. With this, it would offer a better prognosis for patients and provide them with a greater quality of life.