Regulation of adipogenesis by selenium in vitro

Julie Lynn Wiacek, Purdue University

Abstract

Obesity is linked to the development of cardiovascular disease and cancer. Therefore, finding novel methods to control this epidemic is critical. Increased adiposity stems from adipocyte hyperplasia and hypertrophy. Adipogenesis, the conversion of preadipocytes into mature adipocytes, is responsible for increasing fat cell number and has been effectively modeled in vitro . Research has proposed that finding ways to inhibit adipogenesis, or adipocyte differentiation, is an effective means to combat obesity. Concomitant with adipogenesis is an increase in endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Inhibition of the UPR has been shown to attenuate adipocyte differentiation. Selenium (Se), an essential micromineral, has shown promise in preventing and treating many medical conditions secondary to obesity. Furthermore, research has suggested that Se, through selenoproteins, can attenuate the UPR. However, its role in obesity development has never been investigated. Therefore, our research goal was to examine Se's impact and associated mechanism of action on adipogenesis in vitro. We hypothesized that Se would modulate the UPR during differentiation, thereby inhibiting adipogenesis. In our research, we found that inorganic selenate was less toxic than inorganic selenite and organic methylseleninic acid in 3T3-L1 cells. Selenate was also the most potent anti-adipogenic agent as evidenced by the dose-dependent decrease in intracellular lipid accumulation. Complete inhibition was observed at 50 microM, at which there were no negative effects on cell viability. We revealed that selenate's inhibitory action is limited to the early stage of adipogenesis where it reduced mRNA expression of adipogenic transcription factors such as, peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT-enhancer-binding protein alpha (C/EBPalpha). Selenate also increased protein levels of selenoprotein S (SEPS1), an ER resident selenoprotein. Concurrently, selenate lowered mRNA expression of ER stress markers, C/EBP homologous protein (CHOP) and X-box binding protein 1 (XBP1). Protein and mRNA levels of glucose-regulated protein 78 (GRP78) were also downregulated. Taken together, our results are the first to suggest that selenate may serve as an anti-adipogenic agent in vitro possibly through UPR attenuation. Furthermore, our study supports a role for dietary compounds, such as Se, in the prevention of adipose tissue expansion during obesity development.

Degree

M.S.

Advisors

Kim, Purdue University.

Subject Area

Food Science

COinS