A new study discovered a promising connection between the inhibition of the CD44 gene and the reduction of obesity and metabolic dysfunction in mice.
Researchers found that removing the CD44 gene, which plays a role in cellular adhesion and movement, decreased fat accumulation in white adipose tissue and improved insulin sensitivity. The findings, published as a prepress proof in The American Journal of Pathology, highlighted a potential target for developing treatments for obesity and metabolic syndrome.
CD44, commonly studied for its role in cancer and inflammation, is now recognized as a contributor to fat-cell (adipocyte) growth and differentiation. In mice, CD44 appears to regulate fat cell formation or adipogenesis via the TPH2 enzyme, an important factor in serotonin synthesis. This enzyme affects how fat cells grow and respond to energy intake, making it a target for obesity research.
The study observed that removing CD44 in high-fat diet (HFD) mice resulted in smaller fat cells, less fat buildup in the liver, and a significant decrease in markers of metabolic disease. The researchers identified TPH2, a gene involved in serotonin production, as a mediator in this process. In normal fat cells, CD44 promotes the expression of TPH2, which increases serotonin levels and, consequently, enhances fat accumulation. However, when CD44 is absent, TPH2 expression drops, reducing serotonin and adipocyte growth.
The research team also examined the effects of pCPA, a TPH2 inhibitor, in mice fed an HFD. The results were encouraging as mice treated with pCPA gained less weight and showed improved glucose metabolism compared with untreated counterparts. Notably, the impact of pCPA on reducing adipogenesis was consistent with observations in CD44-deficient mice, underscoring the TPH2/serotonin pathway’s role in fat regulation.
While further studies are needed, the implications for human health are promising. Targeting the CD44/TPH2 pathway could provide new therapies for obesity-related conditions, potentially allowing for treatments that prevent or reduce fat storage without impacting normal metabolic function.
The findings suggested that modulation of serotonin levels in fat tissue could represent a valuable approach to managing obesity, particularly as rates of metabolic diseases continue to rise globally.
