Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis

Area of Science:

• Biochemistry
• Cell Biology
• Regenerative Medicine

Background:

• Hyaluronan-binding proteins, including CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM), are crucial regulators of stem cell differentiation.
• CD44 expression is essential for subcutaneous adipogenesis (fat formation).
• RHAMM expression, conversely, inhibits this process.

Purpose of the Study:

• To investigate the role of RHAMM in subcutaneous adipogenesis.
• To develop RHAMM function-blocking peptides as a tool to promote adipogenesis for clinical and tissue engineering applications.

Main Methods:

• Screening of RHAMM function-blocking peptides using rat bone marrow mesenchymal stem cells, mouse pre-adipocytes, and human subcutaneous pre-adipocytes.
• In vitro assessment of adipogenesis using Oil red O staining and adiponectin production.
• In vivo evaluation of peptide efficacy in promoting adipogenesis in rat dorsal and mammary fat pads using micro CT imaging, histology, and gene expression analysis.

Main Results:

• RHAMM function-blocking peptides significantly increased subcutaneous fat pad area and mammary fat pad size in rats.
• The observed increase in fat content persisted for over 5 weeks.
• Peptide treatment led to increased expression of key adipogenic genes, including PPARγ and C/EBP.

Conclusions:

• RHAMM actively suppresses subcutaneous adipogenesis, while blocking its function promotes fat formation.
• RHAMM function-blocking peptides represent a novel, minimally invasive therapeutic strategy for lipodystrophic diseases.
• These peptides can serve as a complementary tool for subcutaneous fat augmentation techniques.