Obesity and diabetes are common diseases in the United States. Microproteins, which are small proteins, have not been considered in research before, but recent research shows that they play a crucial role in metabolism. Salk Institute researchers found that both white and brown fat contain numerous unknown microproteins, and one of these microproteins, Gm8773, has the ability to increase appetite in mice.

The findings were recently published in the journal Cell Metabolismmay lead to weight gain treatment for certain diseases, such as during cancer chemotherapy. The team’s discovery of these microproteins also provides the scientific community with valuable resources for further study of microproteins.

Co-author of the study and Dr. “Better understanding the processes that regulate obesity and metabolic status is vital to enable better treatments in the future,” says Salk Professor Alan Sagatelian, chair of the Frederick Paulsen Chair. “Having this list of microproteins will help the field of metabolism identify new players in various metabolic diseases. And we have shown a nutrition-promoting bioactive microprotein as well as other microproteins involved in fat metabolism.”

Adipose tissue secretes many different proteins to regulate nutrition, energy balance and heat production. Known as “bad fat”, white fat is usually found just under the skin and in the abdomen. This type of fat acts as an energy store and has been linked to obesity and other diseases caused by being overweight. In contrast, brown fat or “good fat” is found around the shoulders and along the spinal cord. Brown fat is associated with proper nutrition, exercise, and health.

In this study, scientists used innovative genomic techniques to study brown, white, and beige fat (another type of fat with similar properties to both white and brown fat) in mouse cells. They identified 3,877 genes that produce microproteins in both white and brown fat. Additionally, they examined the levels of these genes in mice fed a high-fat Western diet and linked hundreds of microproteins to changes in adipose tissue metabolism. Overall, the analysis highlights for the first time many microproteins that may be metabolically relevant.

“We’ve provided a roadmap for how best to use our data to connect and ultimately characterize the role of microproteins in key metabolic pathways,” says first author Tomás Martinez, a former postdoctoral researcher in Sagatelian’s lab and now an associate professor at UCLA. .

The team also focused on a microprotein called Gm8773, which is located in the brain’s powerhouse called the hypothalamus. The location of the microprotein in the brain suggests it may play a role in appetite. Indeed, when scientists injected Gm8773 into obese mice, the mice consumed more food. There is also a human gene similar to Gm8773, called FAM237B, and this gene may act similarly to promote feeding in humans. According to the researchers, this microprotein could eventually be turned into a therapeutic substance that will promote weight gain in those experiencing extreme weight loss.

“The new microproteins presented in our study are exciting discoveries for the study of metabolism and fat biology,” said co-author Chris Barnes, formerly of the Novo Nordisk Research Center Seattle, Inc. and now 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 laboratories, and that this work will lead to the discovery of new mechanisms in biology.”