Researchers Have Come Up With A Promising New Way To Treat Obesity By Genetically Modifying Fat Cells
Researchers at UT Southwestern Medical Center discovered that genetically modifying fat cells in obese mice to produce higher levels of the glucose-dependent insulinotropic polypeptide receptor (GIPR) led to significant weight loss. In fact, the mice shed over a third of their body weight through an energy-burning process.
The results of their latest study suggest that GIPR, once seen as a secondary factor in widely used weight loss medications, could play a more prominent role in future obesity therapies.
“Our study brings GIPR in fat cells to light as a meaningful target for the development of future therapeutic interventions for the treatment of obesity and its associated metabolic diseases,” stated Christine M. Kusminski, the study’s leader and corresponding author.
Over 100 million adults in the United States have obesity, and more than 22 million U.S. adults have severe obesity, according to the CDC.
Obesity has been linked to other serious chronic diseases as well, such as heart disease, diabetes, osteoarthritis, and some forms of cancer.
In recent years, several drugs targeting the glucagon-like peptide-1 receptor (GLP-1R) have received FDA approval for treating obesity.
Research has shown that these medications work by influencing key areas of the brain responsible for controlling appetite.
The FDA also recently approved a new wave of weight-loss medications that target both GLP-1R and GIPR. These medications have shown remarkable results in helping individuals with type 2 diabetes and obesity lose weight.
Nonetheless, scientists are still working to fully understand how GIPR contributes to enhancing the effectiveness of GLP-1R-based treatments.
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GIP, a hormone produced in the gut, plays a vital role in metabolic processes. To investigate its influence on body weight, the researchers studied mice with fat cells genetically modified to produce excess GIPR.
Once the team activated additional GIPR in the fat cells of obese mice, the animals experienced rapid and significant weight loss. More specifically, they lost around 35% within just two weeks.
Plus, among mice of normal weight, activating these extra receptors made them resistant to obesity, even when they were given a high-fat diet.
The team examined changes in gene and metabolic pathways within the fat tissue to understand how GIPR activation in fat cells caused such outstanding weight loss.
They discovered that when the fat cells overproduced GIPR, there was heightened activity in the sarco/endoplasmic reticulum calcium ATPase (SERCA) pathways, which consume energy to move calcium within the cells.
Further study revealed that the additional GIPR caused fat cells to consume extra ATP, an energy-carrying molecule, without actually transporting calcium.
Known as futile calcium cycling, this inefficient process resulted in much more energy expenditure, which helped drive the weight loss observed in mice with overproduced GIPR in their fat cells.
After several weeks, when the researchers turned off the extra GIPR production, the mice actually didn’t regain any of the weight they had lost, either. Dr. Kusminski detailed how the mice seemed to develop a sort of “metabolic memory,” which helped shield them from obesity even after the extra GIPR was no longer active in their fat cells.
This outcome contrasts with human patients who take current weight-loss medications because when they stop the drugs, they often experience rapid weight regain.
“Having a better understanding of how GIPR operates in fat cells helps to explain why targeting GIPR, in addition to GLP-1R, causes individuals with obesity to lose more weight than those who take GLP-1R drugs,” concluded. Dr. Kusminski.
“Furthermore, drugs that focus on the GIPR alone, or as a critical part of multi-agonist drugs, could represent a powerful approach to helping people lose weight.”
To read the study’s complete findings, which have since been published in Cell Metabolism, visit the link here.
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