The crosstalk between platelets and body fat: A reverse translational study.

BACKGROUND & AIMS: Our previous study found that platelet counts were positively associated with body fat percentage in human. In the present study, we conducted a reverse translational study to explore the role of platelets in modulating pre-adipocyte proliferation in mice.

METHODS

Mouse pre-adipocyte cell line (3T3-L1) and human pre-adipocytes harvested from female subcutaneous fat were used. Pre-adipocytes were co-cultured with platelets or platelet releasate, which were isolated from mice or humans. The cell viability and proliferative ability of the pre-adipocytes were examined by MTT and flow cytometry assays. Western blotting analysis was used to determine the phosphorylation levels of proteins in the mTOR pathway.

RESULTS

The number of platelets in the adipose tissues from obese mice was significantly higher than that from lean mice. Platelets and collagen-activated platelet releasate stimulated the proliferation of human pre-adipocytes and 3T3-L1 cells in vitro. Besides, platelets from obese mice were more potent in stimulating pre-adipocyte proliferation than those from lean control mice. Mechanistically, platelets enhanced pre-adipocyte proliferation through the acceleration of cell cycle progression from G0/G1 to S phase cell cycle progression. At the molecular level, platelets promoted pre-adipocyte proliferation through mTOR pathway-mediated upregulation of cyclin D1 expression.

CONCLUSION

In conclusion, platelets and platelet releasate play an important role in the proliferation of pre-adipocytes. Our study may provide new clues and the molecular mechanism of the causal pathways between platelets and body fat to explain the finding we observed in population study.