Animal experiments prove the efficacy of an anti-obesity therapeutic


There is a worldwide concern of the epidemic of obesity. Obesity has been connected with a wide range of health problems. Therefore, a lot of pharmaceutical companies and research institutions are trying to seek effective measures for obesity intervention.

A research group at Amgen Inc. has now designed a modified protein that has weight-reducing effect. When tested in mice, rats, and monkeys, the modified protein led to weight loss as well as decreased blood levels of insulin and cholesterol. The encouraging results highlight the need for further research into the effect of the modified protein on obesity.

Growth/differentiation factor 15 (GDF15), also referred to as Macrophage inhibitory cytokine-1 (MIC-1), is a member of the transforming growth factor beta superfamily, which modulates inflammatory and apoptotic pathways during injury and disease processes.

A growing body of evidence suggests that GDF15 levels increase after tissue stress and injury, and increased protein levels correlate with body weight loss in many diseases. These studies suggest GDF15 as a candidate anti-obesity therapeutic. But a big problem that limits its application is that the body tends to clear extra GDF15 protein rapidly. In the new study, Amgen researchers solved this problem by adding an antibody fragment to the protein. This modified protein, named GDF15-Fc fusion, is more stable in the body.

Amgen researchers first used multiple methods to confirm that GDF15 levels were elevated in obese mice, rats and humans compared with the lean controls. Using a variety of metabolic disease models in mice, rats and monkeys, the researchers proved that overexpression of GDF15 and recombinant GDF15 treatments helped reduce food intake and body weight and benefited metabolic health.

The researchers engineered GDF15 to make it could stay longer in the body. The modified version of GDF15, known as GDF15-Fc fusion, has a longer half-life. Further research is required to test the efficacy and safety of GDF15-Fc fusion proteins in the treatment of obesity and a wide range of connected diseases.

The study (Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys) appears in the latest issue of Science Translational Medicine.
 
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