Humic acid extracted from Blackfoot disease-endemic well water induces adipocyte differentiation of C3H10T1/2 fibroblast cells: a possible mechanism leading to atherosclerotic-like plaque in Blackfoot disease

A unique peripheral vascular disease named "Blackfoot disease" (BFD) is endemic on the southwest coast of Taiwan. Clinically, the signs and symptoms of BFD are similar to those of arteriosclerosis and Buerger disease. Humic acid has been proposed as a causative factor in BFD; however, the relationship between humic acid and atherosclerotic-like plaque associated with BFD remains unclear. In this study, we investigated the effects of humic acid extracted from Blackfoot disease-endemic well water (BFD-HA) on cultured C3H10T1/2 fibroblasts, a murine embryonic cell line. Our present data demonstrate that C3H10T1/2 cells were arrested at the G, phase and subsequently differentiated to adipocytes after treatment with BFD-HA. The adipocyte differentiation of C3H10T1/2 cells induced by BFD-HA was also accompanied with increased glycosaminoglycan production. These results suggest that a large lipid accumulation of arterial blood vessels in BFD patients may be linked in part to the adipocyte differentiation of vascular fibroblasts induced by BFD-HA.