New protein discovered in the fight against obesity

Geschatte leestijd: 2 minuten Chinese researchers have discovered a protein that could be used as a tool in the fight against obesity. The molecule called GDF15 appears to be decreased in people and animals with overweight. Administering the protein promotes weight loss and healthier food choices.

GDF15

Last week we shared the results of former minister Jan Kees de Jager. In that article, I defended the use of a surgical procedure in cases of severe obesity. The end justifies the means in that case, but that doesn’t mean that surgical interventions and associated side effects should be avoided if possible. With that in mind, American researchers went in search of alternatives [1]. They looked at the various proteins involved in metabolism. One of the proteins that seemed interesting for this purpose was the growth factor GDF15 and its function. GDF15 plays a role in combating infections and cell death [2,3]. However, the researchers also observed that GDF15 occurs in lower amounts in people, mice, and rats with overweight. Yumei Xiong and colleagues decided to develop therapies based on the molecule. When they administered GDF15 to overweight mice (both by diet and genetically), this led to a decrease in weight. The mice also ate less after administration, and their insulin levels decreased. However, because GDF15 is difficult to produce and has a short half-life (so it is not effective in the body for long), the researchers also experimented with two so-called fusion proteins based on GDF15. These turned out to be more stable and better able to lead to higher levels in the body. Both designer proteins reduced body weight in overweight monkeys.

Healthier Taste

Another interesting finding was that mice that received increased levels of GDF15 in this way opted for a healthier type of food. When given the choice between a standard meal or a meal containing many more calories, the GDF15 mice chose the standard meal, while the untreated mice chose the heavier meal. The researchers found that GDF15 activates a population of nerve cells called AP neurons. These form part of the so-called ‘brain-gut axis’. In this communication between the brain and intestines, substances that reach the intestines can send a signal to the brain, such as in this case a signal that influences meal choice. However, they indicate that more insight is needed, particularly regarding the cell receptor of GDF15. We can almost weekly share insights like this. The question is, of course, when these will translate into effective tools for weight loss in practice.

References

1. Yumei Xiong, Kenneth Walker, Xiaoshan Min, Clarence Hale, Thanhvien Tran, Renee Komorowski, Jerry Yang, Jasmine Davda, Noi Nuanmanee, Dao Kemp, Xiaozhen Wang, Hantao Liu, Silke Miller, Ki Jeong Lee, Zhulun Wang, Murielle M. Véniant. Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. Science Translational Medicine, 2017; 9 (412): eaan8732 DOI: 10.1126/scitranslmed.aan8732
2. Bootcov, Michelle R; Bauskin, Asne R.; et al. (1997). “MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily”. PNAS. 94 (21): 11514-11519.
3. Zimmers T, Jin X, Hsiao E, McGrath S, Esquela A, Koniaris L (2005). “Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury”. Shock. 23 (6): 543–8.