LA JOLLA, Calif. — Scientists have discovered over 3,800 small proteins involved in metabolism in the bodies of mice. However, one microprotein in particular, Gm8773, appears to stimulate appetite, encouraging the animals to eat. Thanks to the discovery, the microprotein could provide a new approach to improving weight gain among people battling cancer and other metabolic diseases.
Despite how common obesity and metabolic diseases like diabetes are in the United States, there is still a huge gap in knowledge when it comes to studying microproteins. These are tiny proteins found in brown and white fat that appear to play a role in metabolism.
“It is vital to better understand the processes that regulate obesity and metabolic health in order to provide improved therapies for the future,” says Alan Saghatelian, a professor at the Salk Institute for Biological Studies and co-author of the study, in a statement. “Having this list of microproteins will aid the field of metabolism in identifying new players in a variety of metabolic diseases. And we’ve demonstrated one biologically active microprotein that promotes feeding, as well as other microproteins that are involved in fat metabolism.”
Underneath fat tissue lies different proteins involved in feeding, energy balance, and heat production. There are two types of fat. White fat is nicknamed “bad fat” and is typically responsible for the bulge you see around the stomach area. This fat acts as an energy storage space when energy is being produced but not used up in the body, causing excess weight. Brown fat, on the other hand, is known as the “good fat.” This type of fat is usually found around the shoulders and spinal cord area. Despite its name, brown fat helps the body and is made when someone is enjoying good nutrition, exercise, and health.
The study authors analyzed the genes of brown, white, and beige fat (a type of fat with features of both white and brown fat) in mouse cells. There were 3,877 genes that created microproteins from white and brown fat. These microproteins were involved in changes to fat tissue metabolism when they came from mice fed a high-fat Western diet.
“We’ve provided a roadmap on how to best use our data to link and eventually characterize the roles of microproteins in fundamental metabolic pathways,” comments Thomas Martinez, a former postdoctoral fellow in Saghatelian’s lab who is now an assistant professor at UC Irvine.
The team paid special attention to Gm8773, which is found in the hypothalamus. The hypothalamus is a brain area that regulates feeding. Administering the Gm8773 microprotein to obese mice caused them to eat more, suggesting it plays a role in appetite. The human equivalent of Gm8773 is a human gene called FAM237B, which the study authors predict has a similar role in eating behavior.
“The new microproteins presented in our study are exciting discoveries for the field of metabolism and for the study of fat biology,” says Chris Barnes, a researcher and head of proteomics at Velia Therapeutics. “We hope that this resource will be used to generate numerous new experimental hypotheses for the scientific community to test in their own labs, and that this work leads to the identification of novel mechanisms in biology.”
Ideally, the researchers believe Gm8773 and its human counterpart will help scientists create a way to stimulate metabolism and appetite, especially for cancer patients dealing with the side-effects of chemotherapy.
The study is published in the journal Cell Metabolism.