Isorhamnetin at Physiologically Attainable Nanomolar Concentrations Inhibits Adipocyte differentiation and Lipid Droplet Accumulation in vitro

Differentiation of preadipocytes into adipocytes is a major step leading to obesity. This study examines the effects of isorhamnetin, a metabolite of quercetin, at physiological and supraphysiological concentrations on the differentiation of 3T3-L1 pre-adipocyte to adipocyte. Comparison was made with the effect of quercetin on 3T3-L1 differentiation under the same conditions. Cell viability during adipocyte differentiation for 8 days in the presence of isorhamnetin and quercetin was above 94% and 97%, respectively. Oil Red O staining showed significant differences (P < 0.05) between the effect of isorhamnetin or quercetin on cytoplasmic lipid droplet accumulation and control untreated cells. Isorhamnetin at physiologically attainable concentrations was more effective than quercetin in inhibiting cytoplasmic lipid droplet accumulation. Neither isorhamnetin nor quercetin had an effect on the expression of macrophage chemoattractant protein -1 (MCP-1). CCAAT/enhancer binding protein α (C/EBP-α) was down-regulated by isorhamnetin. Compared to control, isorhamnetin or quercetin decreased PPAR-γ 1 and 2 expressions. The data indicate that isorhamnetin more than quercetin was effective at physiologically attainable concentrations in reducing lipid accumulation in 3T3-L1 pre-adipocytes.