Study pinpoints a protein that's a key regulator of body weight
By studying the behavior of a protein tightly linked with a wide range of cancers, scientists have uncovered the role it plays in regulating body weight. The discovery deepens our understanding of the way our bodies respond to food, or lack thereof, and opens up new possibilities when it comes to the treatment of metabolic disorders.
The breakthrough comes from medical scientists at Yale University, who were exploring the way a protein called augmentor-alpha contributes to human cancers. The protein is known to bind to a molecule called anaplastic lymphoma kinase receptor (ALK) that mutates and drives a range of cancers, and in an effort to learn more, the researchers sought to identify where the protein was most abundant.
Through experiments on mice, the scientists found augmentor-alpha was most strongly expressed in a brain region called the hypothalamus, which plays a role in many important functions including regulation of temperature, stress response and metabolism. More specifically, the scientists found augmentor-alpha expressed in high levels in what are called agouti-related peptide (AgRP) neurons, which are known to promote hunger.
“AgRP neurons are so important for feeling hunger that without them, you wouldn’t eat. You’d die,” said Tamas Horvath, an author of the study. “So when it became clear that augmentor-alpha was dominantly expressed in these neurons, it immediately suggested that augmentor-alpha was involved in metabolism.”
The scientists turned to mice again to explore the relationship between augmentor-alpha and metabolism, and found that placing the rodents on a fasting diet boosted the protein's expression in the AgRP neurons. They then studied mice engineered to be missing the protein altogether, finding that they were thinner and more physically active than regular mice, regardless of whether they ate a high-fat or healthy diet.
During fasting, these mice without the protein were still highly active. This runs counter to what scientists would normally observe during fasting, where mice would usually limit their activity to conserve energy when there is not much food on offer. This suggests that augmentor-alpha is responsible for some important signaling in the context of metabolic function.
“From what we observed in this study, we think one of augmentor-alpha’s roles in the body is to slow down metabolism when there’s a lack of food,” said Schlessinger. “It’s like it is saying, ‘You don’t have food, don’t expend so much energy.’"
These results raise some interesting possibilities around metabolic health. Some cancer drugs that target ALK already inhibit augmentor-alpha, and could therefore be adapted for metabolic disorders where a patient's weight is problematic for their treatment. Conversely, boosting augmentor-alpha could offer a way of treating appetite loss as a side effect of other medicines, or eating disorders such as anorexia.
But because it is highly concentrated in the hypothalamus and this brain region is known to play a role in a variety of bodily functions, therapies that manipulate augmentor-alpha could have wide-ranging effects.
“I think we’re just scratching the surface of augmentor-alpha’s role,” said Schlessinger.
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: Yale University