Physiologically achievable doses of resveratrol enhance 3T3-L1 adipocyte differentiation

Resveratrol is a natural polyphenolic stilbene widely found in grapes, berries, and other plants. Caloric restriction-like effects of resveratrol have been associated with suppressive and apoptotic effects on adipocyte differentiation in vitro when used at high doses (≥ 20 µM), which may not be achievable in vivo. The aim of this study was to investigate the effects of resveratrol at physiologically achievable low doses (1 and 10 μM) on 3T3-L1 adipocyte differentiation.

3T3-L1 preadipocytes were differentiated into adipocytes using a modified adipogenic cocktail in the presence or absence of resveratrol. Differentiation was determined by lipid accumulation and mRNA expression of marker genes. Activation of glucocorticoid receptor (GR) and peroxisome proliferator-activated receptor γ (PPARγ) was determined by transcription factor-mediated reporter assays and mRNA expression of target genes. Protein samples were collected for the study of AMPK activation.

Resveratrol at physiologically achievable doses (1 and 10 µM) significantly enhanced 3T3-L1 adipocyte differentiation although the effect was less pronounced compared with that achieved under optimal differentiation cocktail in vitro. Resveratrol (1-50 µM) dose dependently activated or synergized with the synthetic ligand or adipogenic treatment to activate GR and PPARγ. However, resveratrol induced cell death when used at doses above 10 µM in differentiating cells.

Our results report for the first time that resveratrol at physiologically achievable doses (1 and 10 µM) enhances 3T3-L1 adipocyte differentiation, which supports the emerging paradigm that enhanced adipocyte differentiation may be associated with caloric restriction-like metabolic effects for resveratrol.