Piceatannol Is Superior to Resveratrol at Suppressing Adipogenesis in Human Visceral Adipose-Derived Stem Cells

Abstract

Resveratrol (3,4',5-trans-trihydroxystilbene) and piceatannol (3,3',4',5-trans-tetraphydroxystilbene) are major stilbene compounds that are predominantly present in various natural foods, such as berries and fruits. Both phytochemical compounds are consumed as dietary supplements to prevent various metabolic diseases and for their anti-aging properties. Adipose-derived stem cells from human visceral adipose tissue (vASCs) are a useful in vitro model for evaluating their adipogenic effect. Treatment with resveratrol and piceatannol significantly inhibited lipid accumulation in vASCs. Their effective concentrations were 5, 10, and 20 μM for inhibiting adipogenesis of vASCs. Interestingly, despite the similar chemical structures of the two compounds, piceatannol showed a higher anti-adipogenic effect at 20 μM than resveratrol in vASCs. Moreover, the inhibitory capacity of lipid droplet generation was higher for piceatannol at 20 μM than that of resveratrol. Piceatannol significantly attenuated the expression level of adipogenic markers (e.g., CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2)) compared to resveratrol at the mRNA and protein levels. These results suggest that piceatannol is a superior anti-adipogenic compound compared to resveratrol in the vASC model of visceral obesity.

Keywords: adipogenesis; human visceral adipose-derived stem cells; obesity; piceatannol; resveratrol.

Figure 1

The chemical structure of (a) resveratrol (Res) and (b) piceatannol (Pic). In the structure formula of Res, two aromatic rings are connected by one methylene double bond. Pic is a hydroxyl derivative of Res.

Figure 2

The effect of resveratrol (Res) (a) and piceatannol (Pic) (b) on the cell viability of human visceral adipose-derived stem cells (vASCs). vASCs were treated with the Res and Pic in the presence of adipogenic differentiation medium (ADM) for two days. Cell viability was quantified using the MTT assay and absorbance was measured at 570 nm. Data are expressed as means ± SD from three independent experiments (*** p < 0.001 vs. ADM-treated-group).

Figure 3

(a) Human visceral adipose-derived stem cells (vASCs) were treated with the resveratrol (Res) and piceatannol (Pic) in the absence or presence of adipogenic differentiation medium (ADM) for 14 days and stained with oil red O (ORO). Intracellular lipid accumulation levels were quantified by extracting ORO-stained lipid droplets with 100% isopropanol and the absorbance was measured at 495 nm. Data are expressed as means ± SD from three independent experiments (** p < 0.01 and *** p < 0.001 vs. ADM-only-treated group of the Res treatment groups; ^# p < 0.05 and ^### p < 0.001 vs. ADM-only-treated group of the Pic treatment groups; ^ᶲᶲ p < 0.01). (b,c) Photographs are representative images of the three independent experiments (magnification 10× and 40×). (d) vASCs were treated with Res and Pic in the presence of ADM for 14 days and stained with 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY). Confocal images of fat body stained with BODIPY 493/503, Phalloidin, and 4′,6-diamidino-2-phenylindole (DAPI) to show lipid droplets, actin filaments, and nuclei, respectively.

Figure 4

The effect of resveratrol (Res) and piceatannol (Pic) on the expression of adipogenic differentiation markers in human visceral adipose-derived stem cells (vASCs). (a–c) The relative mRNA expression of adipogenic genes, namely CCAAT/enhanced binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and adipocyte fatty acid binding protein (aP2), were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) on day three after adipogenic differentiation medium (ADM) treatment. Data are expressed as means ± SD from three independent experiments (^### p < 0.001 vs. undifferentiated group; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. ADM-treated group). (d–g) The protein expression of adipogenesis related proteins, namely CEBP/α, PPARγ, and aP2, were analyzed using Western blot on day four after ADM treatment. Data are expressed as means ± SD from three independent experiments (### p < 0.001 vs. undifferentiated group; * p < 0.05 and *** p < 0.001 vs. ADM treated group).