A study conducted by scientists at the University of Texas Health Centre Houston and the University and Science and Technology (UTSC) highlights the dispensable role of agouti-related protein (AgRP) contrary to known facts.
Agouti and Agouti-related protein is a molecule that according to studies plays a role in feeding patterns, increases food uptake and when it is expressed in higher quantities causes overfeeding leading to obesity, the study says.
Many previous studies emphasized the role of Agouti-related protein in metabolism and feeding behavior, such as the paper released by Harvard University in 2011 where scientists used certain techniques to activate agouti-related protein in mice brains and discovered that this activation led to binge eating behaviors and overconsumption of food.
Another paper released in Nature Metabolism in August 2020 proved that chronic activity of Agouti-related protein resulted in overfeeding and obese mice.
The most cited paper that supported the importance of Agouti-related protein used diphtheria toxin to kill the agouti neurons after which mice models stopped feeding and died.
The Dispensability of Agouti-Related Protein
In the study conducted in the US and China, scientists programmed AgRP neurons to express receptors for diphtheria toxins and then further administered diphtheria toxin in doses adequate to kill AgRP neurons. The results of the study astounded them. They did not find any significant change in weight and feeding levels as compared to their control mice.
To confirm their observations they replicated the previous study which proclaimed that diphtheria toxin kills AgRP neurons. Dr. Tong from the University of Texas commented that a high dose of the diphtheria toxin killed both the AgRP-expressed and wild-type (control) mice. Dr. Tong and team theorized that previous observations where the mice died due to AgRP neurons being damaged by diphtheria toxin were due to its generic activity.
Dr. Zhan’s lab from the University of Science and Technology tackled this with another method. He implemented the use of the caspase-3 gene. Caspase-3 promoted apoptosis i.e. cell death. Dr. Zhan programmed the AgRP neurons to express the caspase-3 protein causing its death. Similar to Dr. Tong’s observations they did not find significant changes in weight and feeding behavior. Dr. Zhan hypothesized that Agouti-related protein may play a role in feeding behavior, pattern, and metabolism in cases of food scarcity.
Implications of the Study
Obesity today is considered an epidemic, killing nearly 4 million people each year. It is the root cause of many diseases such as Type 2 diabetes, heart attack, high blood pressure, stroke, cancer, and reproductive disorders such as PCOS, infertility, endometriosis, and more.
Understanding the neural networks, genes and proteins crucial in modulating hunger and feeding patterns could aid in developing novel therapies for people with eating disorders, obesity, weight loss plans for individuals, developing nutrition plans, and more.
Dr. Zhan’s next goal is to study how feeding behavior works and how it can adapt to changes. They want to understand the connections between different appetite-stimulating neurons and find new ways to control feeding.
