Mice lacking ALK7 had abnormally high insulin levels and accumulated less fat and weight when fed a high-fat diet, according to two studies in PNAS.

Scientists showed in two recent studies that will be published in Proceedings of the National Academy of Science that a growth factor receptor called ALK7 plays important roles in the regulation of body fat deposition as well as the release of insulin from beta-cells in the pancreas.

Using mutant mice lacking ALK7, scientists found that the mice developed abnormally high levels of insulin in the blood, which with age led to insulin resistance and liver steatosis, a pathological condition in which the liver enlarges and accumulates abnormally high levels of fat.

The team also found that calcium signaling in pancreatic beta-cells was reduced by the actions of the growth factor Activin B through the ALK7 receptor and that blood glucose levels regulate the expression of both Activin B and ALK7. In agreement with these results, mice lacking Activin B also developed hyperinsulinemia to a similar extent as ALK7 mutants.

In the second study, the researchers found that mice lacking ALK7 accumulated less fat and gained less weight than their normal counterparts when fed a high-fat diet. They discovered that another growth factor called GDF3 could also signal via the ALK7 receptor and that mice lacking GDF3 showed similar defects in fat deposition and weight gain to the ALK7 mutants. Intriguingly, however, mutant mice consumed equal amounts of food as their normal counterparts during the experiment.

These results show that lack of ALK7 or GDF3 improves energy balance in the body under regimes of high caloric intake, says professor Carlos Ibez at Karolinska Institutet, who lead the two studies.

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