Regulation of adipogenesis and key adipogenic gene expression by nutritional molecules in 3T3 L1 preadipocytes

Abstract

To investigate the function of nutrient molecules (1, 25‐dihydroxyvitamin D (1, 25‐(OH)2D3) and retinoic acid (RA)) in regulation of adipogenesis, adipocyte differentiation and key adipogenic gene expression were studied in 3T3‐L1 preadipocytes. Lipid accumulation was measured by Oil Red O staining and expression of key adipogenic genes was quantified using quantitative real‐time PCR. Adipogenic responses to 1, 25‐(OH)2D3 or RA were determined on days 2–10 after induction of adipogenesis with the traditional hormonal cocktail ± 1, 25‐(OH)2D3 or RA. In response to 1, 25‐(OH)2D3 (10−7, 10−8, 10−9 M), lipid accumulation and the expression of PPARγ, C/EBPα, FABP4 and SCD‐1 were inhibited through day 10. In response to RA (10−6, 10−7 M), lipid accumulation and the expression of these genes were inhibited through day 8, rebounding to control levels by day 10. The greatest inhibitory effect was upon expression of FABP4. However, expression of SREBP‐1c was not affected. The lowest concentrations of 1, 25‐(OH)2D3 or RA tested did not affect adipocyte differentiation or expression of adipogenic genes. These results indicate that 1, 25‐(OH)2D3 and RA inhibited adipogenesis via suppressing adipogenic specific genes, especially FABP4, and suggest that the roles of these nutrient factors in regulating adipogenesis will be informed by further studies of adipogenic specific gene promoter activity.