Scientists in China have found a new potential drug target for weight loss. Blocking a protein called CD44 has been shown to protect against obesity in mice on a high-fat diet, specifically by suppressing the formation of white fat cells.
Semaglutide medications like Ozempic were originally approved to treat type 2 diabetes, but weight loss was noticed as a nice bonus, since it functions as an appetite suppressor. Other versions of semaglutide drugs, like Wegovy, were later approved to specifically treat obesity. Unfortunately they seem to have their share of side effects, including muscle loss and increased risk of a rare form of blindness.
But a new mechanism could lead to a new weight loss drug that complements semaglutide treatments. The focus was the CD44 protein, which has been linked to a variety of cancers and tumor metastasis. Researchers at Nantong University in China suspected it had another role too.
“We previously reported that CD44 deficiency suppresses neuroinflammation,” said Dr. Cheng Sun, lead investigator of the study. “Given the critical role inflammation plays in the progression of obesity and its related complications, including hyperglycemia and insulin resistance, we hypothesized that CD44 might have a significant role in these processes. Therefore, we investigated the potential link between CD44 and metabolic disorders.”
To do so, the scientists engineered mice to lack the gene that produces CD44, and fed them a high-fat diet for two months – covering their teenage-equivalent years and into young adulthood. And sure enough, the gene-edited mice kept a lean figure, while control mice on the same unhealthy diet developed obesity. It also protected against metabolic dysfunction, such as diabetes, that often accompanies high-fat diets.
The team found that CD44 deficiency reduced serotonin levels in white fat tissue, which impaired the formation of new white fat cells. Since it acts directly on unhealthy tissue, drugs that inhibit CD44 could help boost the desired effects of semaglutide drugs, while minimizing some of the risks.
“These findings reveal a novel mechanism linking CD44 to metabolic regulation, thereby offering a novel therapeutic target for obesity and its related metabolic disorders,” said Sun. “This unique mode of action suggests that CD44 inhibitors could serve as a complementary or synergistic treatment alongside GLP-1s, potentially enhancing the overall efficacy of obesity management strategies.”
Of course, it’s still very early for the research, and as with any mouse study there’s no guarantee that this will ever make it to human use.
The research was published in The American Journal of Pathology.
Source: Elsevier