Cell Metabolism Thousands of unknown microproteins have been discovered in fat cells, one of which can increase appetite

Obesity and metabolic diseases, such as diabetes, are very common
in the United States.
Microproteins, known as microproteins, have long been overlooked in research, but new evidence suggests that they play an important role
in metabolism.
Salk's scientists found that both brown and white fat were filled with thousands of previously unknown microproteins and showed that one of them, called Gm8773, increased appetite in mice
.

The findings, published in Cell Metabolism, will take place on January 3, 2023, and could lead to the development of a treatment that helps people gain weight in certain disease situations, such as during
cancer chemotherapy.
In addition, by identifying the presence of these microproteins, the team also provides a valuable resource
for the scientific community to study microproteins.

"To provide better treatments for the future, a better understanding of the regulatory processes of obesity and metabolic health is critical," said Salk Professor Alan Saghatelian, co-corresponding author
of the study.
"Having this list of microproteins will help the metabolic field identify new players
in various metabolic diseases.
" We have demonstrated a bioactive microprotein that promotes eating, as well as other microproteins
involved in fat metabolism.
”

Adipose tissue secretes many different proteins to regulate eating, energy balance, and caloric production
.
White fat, known as "bad fat," is usually found
under the skin and in the abdominal area.
This type of fat acts as an energy reservoir and has been linked to
obesity and other diseases caused by being overweight.
Instead, brown fat or "good fat" is located around the shoulders and along the spinal cord
.
Brown fat is associated
with proper nutrition, exercise, and health.

In this study, the scientists used innovative genomics techniques to detect brown, white, and beige fat, another type of fat with similar characteristics to white and brown fat,
in mouse cells.
They found 3877 genes
that produce microproteins in white and brown fats.
In addition, they explored 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 a number of microproteins
that may be associated with metabolism.

"We have provided a roadmap on how best to use our data to connect and ultimately characterize the role of microbial proteins in basic metabolic pathways," said first author Thomas Martinez, a former postdoc in Saghatelian's lab and now an assistant professor
at the University of California, Irvine.

The team also focused on a microprotein called Gm8773, which is located in the brain's feeding center, the hypothalamus
.
The location of this microprotein in the brain suggests that it may play a role
in appetite.
In fact, when the scientists injected obese mice with Gm8773, the mice ate more food
.
There is also a human gene similar to Gm8773 called FAM237B, which can also play a similar role in the human body, promoting eating
.
According to the researchers, this microbial protein could eventually be developed as a treatment to promote weight gain
in those who are experiencing extreme weight loss.

"The new microproteins presented in our study are exciting findings in the field of metabolism and adipobiology," said co-corresponding author Chris Barnes, who previously worked at the Novo Nordisk Research Center in Seattle and is now head of
proteomics at Velia Therapeutics.
"We hope that this resource will be used to generate a large number of new experimental hypotheses for the scientific community to test in its own laboratories, and this work will lead to the identification
of new mechanisms in biology.
"

In the future, the scientists plan to develop tools to study the effects of Gm8773 and FAM237B, eventually developing a treatment
that can increase human appetite.

Profiling Mouse Brown and White Adipocytes to Identify Metabolically Relevant Small ORFs and Functional Microproteins