Exploring Novel Environmental Link to Obesity: Role of Parabens in Adipogenesis <i>in vitro</i> and <i>in vivo</i>

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. The extent of the exposure is reflected by the frequent detection of these compounds in urine samples in the general population. Moreover, parabens have been detected in human serum, milk, placental tissues and breast tumor tissues. Parabens have been shown to preserve estrogenic/antiandrogenic effects, and can activate peroxisome proliferator-activated receptors. Therefore, they are considered endocrine disrupting chemicals (EDC). Here, the effects of parabens on adipogenesis in vitro and in vivo were investigated. We report that (1) parabens promote adipogenesis (or adipocyte differentiation) in murine 3T3-L1 cells through activation of nuclear receptor peroxisome proliferator-activated receptor γ and glucocorticoid receptor; (2) the adipogenic potency of parabens is increased with increasing length of the linear alkyl chain in the following potency ranking order: methyl- < ethyl- < propyl- < butylparaben; (3) parabens, butyl- and benzylparaben in particular, also promote adipose conversion of human adipose–derived multipotent stromal cells; (4) oral feeding of parabens in C57B6/J mice increase adiposity with altered metabolic biomarkers; and (5) exposure to parabens enhances adipocyte differentiation, but suppresses osteocyte and chondrocyte differentiation from a multipotent stem cell line. The results suggest that parabens may contribute to adipogenesis, through enhancing differentiation of predetermined preadipocytes, as well as through modulating the multipotent stem cells towards adipose lineage.