Nature: Chinese scientists led the discovery of 1 protein that can "ignite" brain leptin

Maintaining a healthy weight can be a challenge
for many people.
According to the Centers for Disease Control and Prevention, the prevalence of obesity in adults 20 years of age and older in the United States is 42 percent
.
Obesity-related diseases, including heart disease, stroke, type 2 diabetes and certain types of cancer, are the leading causes
of preventable premature death.

To find strategies to help people reach and maintain a healthy weight, researchers at Central South University's Xiangya Second Hospital, Baylor College of Medicine, and the University of Texas San Antonio Health Science Center investigated how activity is regulated by leptin, which is involved in controlling appetite and energy expenditure
.
Through studies in mouse models, the team found that the Grb10 protein promotes leptin activity in the brain, which opens up the possibility
of developing new methods of treating obesity based on Grb10.
The study was published in the journal Nature Metabolism
.

Connections between adipose tissue and the brain

One way for the body to control weight is by using leptin
, which is produced by adipose tissue.
The more fatty tissue the body, the more
leptin it produces.
Leptin reaches the brain and tells specific neurons how much
fat is stored in the body.
A large amount of leptin tells the brain that there is a lot of fat storage
.
In response, the brain triggers behaviors that suppress appetite and increase energy expenditure, which leads to decreased adipose tissue and weight loss
.
When all is normal, leptin-mediated feedback loops between adipose tissue and the brain lead to a consistently healthy weight
.

"Leptin's ability to prevent excessive weight gain by suppressing appetite and simultaneously increasing energy expenditure makes it a promising treatment for obesity," said
co-corresponding author Dr.
Yong Xu, professor of pediatric nutrition and molecular and cell biology at Baylor University.
"Unfortunately, in most cases of diet-induced obesity, leptin supplementation strategies tend to be ineffective, in part due to the development of leptin resistance, a state in which circulating leptin levels remain high, but it does not inhibit food intake and weight gain
.
"

In the current study, Xu and his colleagues looked for molecules that could modulate leptin activity and potentially be used to overcome leptin resistance
.
The team discovered that the Grb10 protein is a new regulator of leptin activity
.

"We found that Grb10 promotes leptin activity," Xu said
.
"One feature of GRB10 with previously discovered leptin regulators is how it works
.
GRB10 binds directly to leptin receptors on neurons to form complexes
.
This combination enhances leptin signaling, helps reduce food intake and increases energy expenditure
.
Other regulators do not bind to leptin receptors, but to
other molecules downstream.
”

After eliminating Grb10 in leptin-response neurons in mouse brains, the animals ate more or reduced energy expenditure and gained
weight.
On the other hand, increasing Grb10 has beneficial effects – it helps animals reduce food intake, increase energy expenditure and lose weight
.
"These results suggest that enhancing Grb10 activity may provide a way to increase leptin signaling, aiding weight loss
," Xu said.
Our findings support the possibility of further investigating the development
of a Grb10-based treatment for obesity.
”

Going forward, the team is interested in further investigating the mechanism of
action of Grb10 in the brain.
"Leptin also regulates mood and other emotional states," Xu said
.
"We wanted to know if Grb10 regulates mood
by interacting with leptin receptors.
"