Scientists found that Growth differentiation factor-15 (GDF15) could cause weight loss, which would be an important drug target for mediating weight loss. GDF15 was a protein which was first identified in mice with prostate tumors and later found the relevance to the weight of people with cancer.  Studies revealed that the regulation of GDF15 in brain would cause weight loss of the mice. Further, how the protein functioned?

      Researchers screened more 4,000 membrane proteins for GDF15, together with fluorescence-activated cell sorting, and discovered that only GDNF family receptor α–like (GFRAL) protein showed the specific affinity to GDF15.  In human brain sections, GDNF expression was localized to two areas of the brain: the area postrema and nucleus of the solitary tract. GFRAL was a receptor with alone functioning on brain development. After being treated with GDF15, GFRAL was increasingly expressed and then stimulating the RET phosphorylation. RET could be a coreceptor with the GDNF receptor family to form a complex.

      Targeted deletions Gfral of the mice would cause weight increasing and aggravate the glucose intolerance, even fed a diet with high fat or control the exogenous GDF15. Nonhuman primates injected with a single dose of HAS-GDF15, which was a recombinant between the human serum albumin and GDF15, were shown a decrease in food intake for two weeks. If treated with HAS-GDF15 for 4 weeks, the weight of the monkeys would lose up to 4% of their body.

      Being confirmed by different teams, GDF15 and GFRAL were believed as the promising weight loss targets, which still needed to be further studied for clinical applications

      EIAab provides the kit for detecting GDF15 in human, mouse and rat, as well we other GDF factors, like GDF8, GDF9, GDF11 and so on. Please refer to www:eiaab.net. in details.

Reference

A Shoemaker. Learning from cancer to promote weight loss. Sci Transl Med., 2017, 9(408): eaao6131. DOI: 10.1126/scitranslmed.aao6131