The body’s own hormone Fibroblast Growth Factor 21 (FGF21) regulates appetite and has a positive effect on the metabolism. Researchers have now made an antibody that binds to the same receptors as the hormone. It has the same effect, but remains available in the body for longer. In a first study they examined its potential suitability as a slimming aid. In fact, a single injection led to a slight weight loss in the subjects and curbed their appetite for sweets – but this effect did not last long.
Depending on the diet, the body produces different amounts of the hormone FGF21. Previous studies have shown that it reaches high levels in the blood, especially on a high-carbohydrate diet. The level is also increased in diabetics and severely overweight people. In a kind of feedback loop, the hormone apparently reduces, among other things, the appetite for further carbohydrates. In both mice and humans, FGF21 injections resulted in decreased feelings of hunger and weight loss. Since the hormone is broken down quickly in the body, regular injections would be necessary for therapeutic use.
Lean through antibodies?
A team led by Amos Baruch from the Californian biotechnology company Genentech has now developed an antibody that binds to the same receptors as FGF21, but remains available in the body for longer. In this way, injections that are much rarer are said to have the same effect as FGF21. In order to test the safety of the experimental antibody and to collect initial indications of its effectiveness, the Genentech researchers recruited 71 overweight but otherwise healthy adults for their phase 1 study. 53 of them received a single injection of the antibody in different doses, 18 people received a placebo instead.
In order to control the calorie intake of the test subjects, they all received the same diet. After a week, people in the antibody group had lost an average of 1.2 kilograms, and people in the placebo group 0.28 kilograms, as the researchers report. The subjects who had received the highest dose of antibody lost the most weight. Apparently, the antibody stimulates the metabolism and leads to higher calorie consumption with the same diet. After the test subjects were able to determine their own diet again, however, the effect quickly offset each other: after three days they had their old weight back.
Less hunger for sweets
With the help of questionnaires and follow-up examinations, the researchers also recorded long-term effects. The blood lipid levels of the subjects from the antibody group improved after the injection. How long the positive effect lasted depended on the dose. People who received the highest dose of antibody had better cholesterol levels than before 60 days after the injection.
In addition, the test subjects were asked to rate their feeling of hunger using a questionnaire. In the weeks after the injection, people in the antibody group reported that they had less appetite for carbohydrates and especially for sweets. This effect was also dependent on the dose injected. Overall, however, there was only a slight influence on the feeling of hunger. After a month, the subjects – apart from those with the highest dose – ate even more on average than before the injection. In another part of the study, on the other hand, the researchers had shown in monkeys that the animals consumed significantly less food after the injection and thus significantly lost weight.
Further studies planned
According to the researchers, the side effects of the experimental therapy were only minor. 41.5 percent of the people from the antibody group reported nausea, 22.6 percent each from diarrhea and vomiting. These side effects were more common with higher doses. “In general, the antibody was well tolerated,” summarize the researchers. “Overall, our data suggest that treatment with the antibody results in weight loss without noticeably reducing appetite, although an aversion to carbohydrate intake is possible.” The company Genentech, a subsidiary of the Swiss pharmaceutical company Hoffmann-La Roche, is already working on further studies, which should show to what extent the antibody therapy is actually suitable for the treatment of overweight patients.
Source: Amos Baruch (Genentech, Inc., South San Francisco) et al., Proceedings of the National Academy of Sciences, doi: 10.1073 / pnas.2012073117