The Grb10 protein offers a potential new approach to the treatment of obesity

For many people, keeping a healthy body weight can be a challenge. According to the Centers for Disease Control and Prevention, among adults 20 years of age and older, the obesity rate is 42% in the U.S. Obesity-related conditions, including heart disease, stroke, Type 2 diabetes and certain types of cancer are among the leading causes of premature, preventable death.

Looking for strategies to help people achieve and maintain a healthy weight, researchers at Baylor College of Medicine, Second Xiangya Hospital of Central South-China University, and University of Health Sciences Center University of Texas at San Antonio investigated the activity of the hormone leptin. , is involved in appetite control and energy consumption, is specified. Working with mouse models, the team discovered that protein Grb10 promotes leptin activity in the brain, opening the possibility of developing new Grb10-based approaches for the treatment of obesity. Research appears in Natural metabolism.

Fatty-brain tissue connection

One way for the body to control weight is by using leptin, which is produced by adipose tissue. The more fatty tissue the body has, the more leptin it makes. Leptin travels to the brain, where it tells specialized nerve cells how much fat is stored in the body. A large amount of leptin tells the brain that there is a large store of fat. In response, the brain activates behaviors that suppress appetite and increase energy use, leading to fat tissue loss and weight loss. When all is well, this leptin-mediated feedback loop between adipose tissue and the brain leads to sustained results. healthy body weight.

Dr Yong Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor, said: “The body’s ability to prevent excessive weight gain by suppressing appetite and at the same time enhancing it energy expenditure makes it a promising therapeutic approach for the treatment of obesity.” . “Unfortunately, leptin-supplementation strategies are often ineffective in most cases of diet-induced obesity, in part due to the development of leptin resistance, a state in which stored leptin levels throughput is still high but not preventable. food amount and increase body weight.”

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

“We found that Grb10 promotes leptin activity,” says Xu. “One feature of Grb10 that sets it apart from previously discovered leptin regulators is its mode of action. Grb10 binds directly to the leptin receptor on neurons, forming a complex. This binding enhances leptin signaling and helps reduce food intake and increase energy expenditure. The other regulators do not bind to the leptin receptor but to other molecules downstream.”

After removing Grb10 in leptin-responsive neurons in the rat brain, these animals ate more or decreased energy expenditure and gained weight. On the other hand, increasing Grb10 has beneficial effects—it helps animals reduce feed intake, increase energy expenditure, and lose weight. “These results suggest that enhancing Grb10 activity may provide a means to increase leptin signaling and help reduce weight“Our findings support further studies on the possibility of developing a Grb10-based obesity treatment.”

In the future, the team is interested in further studying Grb10’s mechanism of action in the brain. “Leptin can also regulate mood and other emotional states,” says Xu. “We wanted to know if Grb10 is involved in mood regulation through interaction with leptin take.”