Engineered proteins lower body weight and cholesterol

Researchers have created engineered proteins that lowered body weight, bloodstream insulin, and cholesterol levels in obese lab animal test subjects, according to a report published in Science Translational Medicine.

The study’s authors say the results could pave the way for urgently needed alternatives to bariatric surgery for treating obesity in humans.

Based on the observation that obese mice, rats, and humans all had elevated serum concentrations of a protein called GDF15, the researchers set out to develop therapies derived from the molecule. In mouse models of obesity, delivery of the GDF15 gene reduced body weights, food intake, and serum insulin levels.

Because GDF15 has a short plasma half-life and is difficult to produce in substantial quantities, the scientists generated two different fusion proteins that were more stable in the circulation and led to higher yields. Both fusion proteins effectively decreased body weights for obese mice and cynomolgus monkeys.

The researchers also showed that the GDF15 regimen altered food preferences in mice. The animals opted for lower calorie food when offered a choice.

The study’s authors conclude that GDF15 activated a population of nerve cells called AP neurons that make up a portion of the gut-brain axis, yet note that further studies to identify the protein’s cellular receptor are needed as potential therapeutics make their way to the clinic and human subjects.