Abstract: Objective: This study was conducted to investigate the potential of blueberry extract to alter the growth, differentiation, and function of human adipose-derived stem cells (hADSCs) and to evaluate its ability of reducing adipose tissue formation and the possible underlying mechanisms. Methods: Human adipose-derived mesenchymal stem cells were isolated and primarily cultured to establish a model cell differentiation in vitro. Blueberry anthocyanin extract at different concentrations was used to intervene in different growth phase of adipocytes. The 3-(4,5-dimethyl-2-thiazolyl)- 2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and the lactate dehydrogenase assay were measured to observe hADSC proliferation in different phases. Oil Red O staining and the AdipoRed assay were used to investigate lipid accumulation in hADCSs during the course of differentiation. The glucose uptake assay was used to investigate glucose uptake in fully differentiated mature human adipocytes. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to measure the expression of adipogenesis-related genes and the secretion of adipocytokines. Results: 1) Treatment with blueberry anthocyanins extract (25–175 μg/mL) for 48 h dose-dependently inhibited hADSCs proliferation in the logarithmic and confluent phases of growth (P < 0.05). It also inhibited hADSCs proliferation in the differentiation phase (P < 0.05), and lipid accumulation in mature adipocytes (P < 0.01). 2) The blueberry extract increased glucose uptake in mature adipocytes in both the absence and presence of 1 μmol/L insulin, and significantly up-regulated the expression of adiponectin (P < 0.05). 3) Peroxisome proliferator-activated receptor γ (PPARγ) expression in differentiating adipocytes was down-regulated by the blueberry extract during differentiation, while it was up-regulated in mature adipocytes (P < 0.05). These results suggest that the blueberry extract can reduce the proliferation and inhibit the differentiation of hADSCs to generate fewer mature adipocytes and less lipid accumulation. Furthermore, the blueberry extract also can maintain or enhance the function of human mature adipocytes by increasing glucose uptake and upregulating the expression of adiponectin and PPARγ. Conclusion: Blueberry anthocyanin extract may have the potential to inhibit obesity.

Key words: blueberry, anthocyanin, human adipose-derived stem cells, differentiation, proliferation, obesity