Scientists have discovered a new hormone that appears to regulate sensitivity to insulin and normalize metabolism. When the researchers administered this newly identified molecule into mice fed a high-fat diet, it not only prevented them from becoming obese, but it also promoted a restoration of metabolic balance, which are two of the beneficial effects associated with exercise. Although research has so far been limited to rodents, the scientists are hopeful that the identification of this hormone could lead to the development of novel ways to treat certain metabolic disorders, like diabetes.
In normal physiology, our food intake is perfectly balanced with our body’s energy requirements. This equilibrium, which is known as metabolic homeostasis, is primarily driven by signaling molecules, called hormones, and brain activity. For example, after we eat a meal, our blood sugar levels increase, triggering a release of insulin from the pancreas. This hormone encourages the muscle and liver to absorb this excess glucose and store it for later use, thus maintaining normal levels of sugar in the blood.
While scientists have built up a fairly detailed picture of the various components that regulate metabolic homeostasis, it seems that there could be another, rather unexpected key player whose role had gone unnoticed until now. This newly discovered molecule, dubbed MOTS-c, is a hormone that is actually encoded by the DNA in our mitochondria, the sausage-shaped powerhouses of the cell. This is in contrast to other described hormones that are encoded by the genes found in our nucleus, which represent the vast majority of our genome. Given that mitochondrial DNA only contains 37 genes, and the fact that mitochondria were long assumed to have little involvement in signaling, this was a fairly surprising finding.
After scrutinizing the potential roles of this newly discovered signaling molecule in metabolism, scientists from the University of Southern California discovered that it predominantly targets muscle tissue, much like insulin. Here, it regulates sensitivity to insulin and also metabolic homeostasis. When sensitivity to insulin wanes, which often happens with age or an unhealthy diet, our cells stop responding to its action and are consequently unable to use it. This so-called insulin resistance is associated with type 2 diabetes, the most common type of diabetes.
To find out more about the effects of MOTS-c on metabolism, the scientists administered it to mice fed a high-fat diet, which normally promotes the onset of obesity and insulin resistance. As described in Cell Metabolism, not only did MOTS-c prevent the development of both of these conditions, but it was also found to prevent the onset of age-dependent insulin-resistance. Given that diet-induced and age-dependent insulin-resistance, alongside obesity, are all risk factors for type 2 diabetes, these results are encouraging.
“This represents a major advance in the identification of new treatments for age-related diseases such as diabetes,” lead researcher Pinchas Cohen said in a news release. Not only that, but these findings also highlight the role of the mitochondria as active regulators of our metabolic system, he adds.
