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Scientists engineer proteins that caused obese animals to lose weight and lower cholesterol

Melissa Healy, Los Angeles Times on

Published in Science & Technology News

As the U.S. obesity rate has galloped toward 40 percent, doctors, drug designers and dispirited dieters have all wondered the same thing: What if a pill could deliver the benefits of weight-loss surgery, but without the knife?

New research brings that hope a notch closer.

Scientists from the biotechnology company Amgen Inc. report they have identified and improved upon a naturally occurring protein that brought about significant changes in obese mice and monkeys, including weight loss and rapid improvements on measures of metabolic and heart health.

The results, published Wednesday in Science Translational Medicine, approximate some of the mysteriously powerful effects of bariatric surgery, in which a surgeon reshapes the stomach and intestinal tract to reduce their capacity. Even before surgery patients lose a lot of weight, most see marked improvements in obesity-related conditions like insulin resistance, high circulating blood sugar and worrisome cholesterol levels.

In mice who got a bioengineered version of the GDF15 protein, the researchers observed even more remarkable changes. These obese mice turned their noses up at extra-rich condensed milk -- a treat that normally prompts mice to gorge themselves. Given the choice, the treated mice tended to opt for standard mouse chow instead, or at least lowered their intake of the fattening condensed milk.

After 35 days, obese mice treated with the bioengineered GDF15 proteins lost roughly 20 percent of their body weight, while mice getting a placebo gained about 6 percent over their starting weight, according to the study. When mice were offered the rich condensed milk, triglyceride levels remained at baseline or rose by about 20 percent in those who got the engineered proteins, while levels more than doubled in the untreated mice. Insulin levels and total cholesterol readings were also significantly better in treated animals than in their untreated counterparts.

The results suggest that the GDF15 engineered by researchers had the power to turn off the kind of reward-driven eating (think doughnuts, milkshakes or bacon cheeseburgers) that drives many of us to become obese, or to regain lost weight.

Some of the weight-loss medications approved in recent years by the Food and Drug Administration -- including Belviq, Contrave, Qsymia and Saxenda -- appear to nudge the food preferences of obese patients in more healthful directions. But bariatric surgery has a pronounced effect in shifting patients' preferences away from high-fat foods. Scientists just don't know why.

The natural version of the GDF15 protein breaks down quickly in the blood. To be an effective weight-loss aid, it would need more staying power.

The Amgen researchers accomplished this by fusing the protein with other agents that would not break down so quickly. The two engineered versions of GDF15 remain biologically active in the blood for longer.

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